Effect of Stress, Depression and Type D Personality On Immune System in The Incidence of Coronary Artery Disease
Effect of Stress, Depression and Type D Personality On Immune System in The Incidence of Coronary Artery Disease
Effect of Stress, Depression and Type D Personality On Immune System in The Incidence of Coronary Artery Disease
Open Access Macedonian Journal of Medical Sciences. 2018 Aug 20; 6(8):1533-1544.
https://doi.org/10.3889/oamjms.2018.217
eISSN: 1857-9655
Review Article
1 2 3 1 4 3
Saideh Masafi , Seyed Hassan Saadat , Katayoun Tehranchi , Roohollah Olya , Mostafa Heidari , Saied Malihialzackerini ,
5* 6
Mahdi Jafari , Ehsan Rajabi
1 2
Department of Psychology, Kish International Branch, Islamic Azad University, Kish Island, Iran; Behavioral Sciences
3
Research Center, Lifestyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran; Department of Psychology,
4
Kish International Branch, Islamic Azad University, Kish Island, Iran; Department of Psychology, Saveh Branch, Islamic
5
Azad University, Saveh, Iran; Department of Clinical Psychology, School of Medicine, Shahid Beheshti University of Medical
6
Sciences, Tehran, Iran; Shahid Beheshty University of Medical Science, Tehran, Iran
Abstract
Citation: Masafi S, Saadat SH, Tehranchi K, Olya R, BACKGROUND: Psychoneuroimmunology (PNI) is the study of the interaction between psychological processes
Heidari M, Malihialzackerini S, Jafari M, Rajabi E. Effect of
Stress, Depression and Type D Personality on Immune
and the nervous and immune systems of the human body. The impact of psychological factors on the immune
System in the Incidence of Coronary Artery Disease. system and the role of this system in Coronary Artery Disease (CAD) are confirmed. Coronary Heart Disease
Open Access Maced J Med Sci. 2018 Aug 20; 6(8):1533- (CHD) is arisen due to the failure of blood and oxygen to the heart tissues.
1544. https://doi.org/10.3889/oamjms.2018.217
Keywords: Psychoneuroimmunology (PNI); Stress; AIM: The present study aimed to describe psychoneuroimmunological processes which contribute to CAD and
Depression; Type D Personality; Coronary Artery Disease
(CAD) CHD progression.
*Correspondence: Mahdi Jafari, MD, MPH, PhD in
Health Psychology, Department of Clinical psychology,
METHOD: Such psychological risk factors like stress, depression and type D personality were investigated here.
School of Medicine, Shahid Beheshti University of Medical Psychoneuroimmunological pathways of all three mentioned risk factors were described for CAD.
Sciences, Tehran, Iran. Tel: +989122166934. E-mail:
drmjafari@sbmu.ac.ir RESULTS: The studies review indicated that stress could be accompanied with myocardial ischemia and help to
Received: 19-Apr-2018; Revised: 08-Jul-2018; rupture. The depression involves in the transfer of stable atherosclerotic plaque to unstable, and type D
Accepted: 18-Jul-2018; Online first: 01-Aug-2018
personality is effective in the initial stages of a CAD.
Copyright: © 2018 Saideh Masafi, Seyed Hassan
Saadat, Katayoun Tehranchi, Roohollah Olya, Mostafa
Heidari, Saied Malihialzackerini, Mahdi Jafari, Ehsan
CONCLUSION: As more information on cardiovascular immunity becomes available, this will provide a better
Rajabi. This is an open-access article distributed under understanding and thus act as the foundation for the potential development of new treatment strategies for
the terms of the Creative Commons Attribution- treatment of cardiovascular disorders.
NonCommercial 4.0 International License (CC BY-NC 4.0)
Funding: This research did not receive any financial
support
Competing Interests: The authors have declared that no
competing interests exist
Open Access Maced J Med Sci. 2018 Aug 20; 6(8):1533-1544. 1533
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paths between the brain and the immune system have Disease (CAD). This process took three months
not well been known [1]. during which total of 38 papers and 108 authoritative
abstracts were collected through Pubmed and Google
The pathophysiological mechanisms effective
Scholar. They ultimately were used to write and
among psychological factors and CAD progress can
prepare for this review.
be related to immunological processes [6]. Recent
research findings indicate that CAD is an important
clinical appearance of psychoneuroimmunological
mechanisms in heart disease progression and acute
coronary syndromes. Kop classifies psychological Results
risk-factors into three groups based on the duration,
that is, their persistent or temporary presence [7]:
Acute triggers such as psychological stress and anger Emotional stress is harmful to the heart.
[8], episodic factors with duration of few weeks to 2 Statistical and clinical studies show that stress can
years such as depression and exhaustion [1], and increase the mortality associated with acute
Chronic Factors such as negative personality myocardial infarction. Of every seven adult Americans
characteristics (enmity in Personality Type A and who suffer heart attacks, one person is experiencing
Personality Type D) and low socioeconomic level. stress. Tobacco and caffeine can increase heart rate
The review studies which relate up to 14 beats per minute, and if they are along with
psychoneuroimmunological factors to coronary heart stress, the increase will reach to 38 beats per minute.
disease will provide helpful information to understand Immune system responses to stress can potentially
the psychoneuroimmunology of heart diseases. In the help to form Atherosclerotic plaque and avulsion or
present paper, we will study the works which take detachment of plaque. Most of the studies on
advantage of the role of stress, depression and psychoneuroimmunology show increased CD8+ cells,
Personality Type D on the immune system while these decreased CD4+ cells, increased blood viscosity and
factors lead to CAD progression. The results here stimulated the immune system versus acute
allow physicians and specialists to realise the psychological challenges [7] [9].
importance of the immune system as a relation Psychological stress activates the SNS, which
between mind and cardiovascular system and pay regulates heart rate and release of catecholamines,
more attention to mental health maintenance to and the HPA axis, which regulates the release of
prevent coronary artery disease. corticosteroids from the adrenal glands [10]. In acute
Therefore, the present paper will study the psychological stress, catecholamines predominantly
following items: affect natural killer (NK) cell circulation. The
relationship between acute stress, SNS and
- Stress effect process in the immune leucocytes are illustrated in Figure 1. In chronic
system and the incidence of coronary artery disease stress, the activity of the HPA axis may decrease,
- Depression effect process in the leading to fatigue and increased activation of immune-
immune system and the incidence of coronary artery mediated inflammation [11] [12].
disease
- Personality Type D effect process in
the immune system and the incidence of coronary
artery disease
And finally, to find a response to the below
question:
Do Stress, Depression and Type D
Personality have different impacts on the immune
system and incidence of coronary artery disease?
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associated with heart rate responses and individual The cytokines produce the multifaceted signs and
differences in sympathetically-driven cardiac stress symptoms of depression [23].
responses were associated with NK and
Cytokines are at the heart of the
proinflammatory cytokine responses to psychological
immunological basis of depression since they provoke
stress [13].
a wide spectrum of neuropsychiatric symptoms when
An acute psychological stressor increases given to human volunteers. The profound effects of
proinflammatory cytokines including mononuclear cell cytokines on mood though, and behaviour was first
IL-1β gene expression and plasma interleukin-6 (IL-6). discovered in the early 1980's. For the first time in
The increased IL-1β gene expression was positively history, physicians had found molecules made by the
correlated with heart rate and systolic blood pressure human body which, when given to humans, produced
reactivity [14]. The cytokines also affect the brain and all the symptoms necessary for the diagnosis of
evoke feelings of malaise, sickness and tiredness [15] depression [24].
[16]. These cytokines can induce the proliferation and
Depressed patients, compared to healthy
migration of smooth muscle cells by stimulating other
controls, have an elevated white blood cell count. A
growth factors that lead to coronary lesions [5] [17].
high white count is called leukocytosis. The white
Mann suggested that the short-term expression of
blood cells (leukocytes) include all of the immune cells
stress-activated cytokines within the heart may be an
found in the blood; consequently, leukocytosis is a
adaptive response to stress, whereas long-term
reliable sign of an activated immune system [24].
expression of these molecules may be frankly
maladaptive by producing cardiac decompensation Increased numbers of monocytes in the blood
[18]. (called monocytosis) of depressed patients were first
reported by Maes et al. and recently confirmed by
Chronic psychosocial stressors increase both
Seidel et al. Monocytes are found in the blood, which
haemostatic factors (e.g. Factor VII) and acute phase
makes them easy to sample and measure. They are
proteins (e.g. Fibrinogen) [19]. Lonely individuals also
the chief source of IL1, IL6, TNF and INFα in the
displayed greater fibrinogen response to stress [20].
blood [25] [26].
Fibrinogen is thought to promote atherosclerosis by
promoting platelet aggregation, enhancing the release Monocytes migrate from the blood into solid
of endothelial-derived growth factors, stimulating tissues where they are transformed into
smooth muscle cell proliferation and increasing macrophages. Macrophages never return to the
plasma and whole blood viscosity [14] [21]. Acute and blood. This means they are rarely evaluated in
chronic stress may activate the coagulation cascade humans because almost all immune system analyses
and lead to thrombus formation and myocardial are done on blood. Nevertheless, in animal
infarction (MI). There is robust evidence from experiments, whenever there is monocytosis, there is
epidemiological studies and meta-analyses that higher macrophage activation someplace in the body. Thus,
levels of acute phase proteins such as CRP and the monocytosis exhibited by depressed patients
fibrinogen predict future cardiovascular death and are indicates that macrophages are activated someplace
associated with low socioeconomic status. in their bodies [24].
Psychological stress is associated with increased
Maes two papers on monocytes cited above
platelet activation and increases the risk of
also found high levels of neutrophils (a condition
cardiovascular disease [20].
called neutrophilia) in the blood of depressed patients.
The relationship between depressive The most severely depressed individuals had the
symptoms and coronary artery disease (CAD) is highest numbers of neutrophils. Neutrophils, the most
mediated in part by immune system parameters. This plentiful of the white blood cells, are members of the
review describes research on the inflammatory arm of the immune system. Neutrophilia
psychoneuroimmunological pathways accounting for is a well-established sign of immune system
the association between depression and CAD and activation. Thus the discovery of neutrophilia in
addresses conceptual and methodological issues [21]. depression is another persuasive piece of evidence
showing that depressed individuals have activated
The Immune-Cytokine Model of Depression
immune systems [24].
(ICMD) is an entirely new concept for understanding
the riddle of depression. This is the only model of The total number of lymphocytes does not
depression to bridge the conceptual and diagnostic appear to be increased in depressed patients.
gap between physical and mental disorders Nevertheless, within the various types of lymphocytes,
[22]. ICMD views depression to be any number of there are very important changes. In a recent study by
chronic physical-biological disorders that have mental- Maes et al., of 106 subjects, there was a significantly
emotional symptoms. From the perspective of ICMD, increased number and percentage of B-lymphocytes
depression isn't a disease, but rather a multifaceted in depressed subjects compared to controls [27]. This
sign of chronic immune system activation. During was confirmed in another study of depressed patients
chronic immune system activation, greater than [28]. B-lymphocytes are the antibody-producing cells.
normal amounts of various cytokines are secreted. (They are called B-lymphocytes because they are
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matured in bone.) Increased numbers and sharp contrast, autoantibodies, clump and identify
percentages of B-lymphocytes are clear signs of self-proteins (that is, proteins which are an integral
immune system activation [24]. part of your own body). Self-proteins, after they are
tagged with autoantibodies, will be attacked and
The T stands for the fact that these
devoured by macrophages and killer lymphocytes. In
lymphocytes mature in the thymus. By secreting
other words, when autoantibodies are produced, the
regulatory cytokines like IL-2 and INFγ, T-lymphocytes
immune system begins attacking the very body it is
exert remarkable control over immune system activity.
supposed to defend. Diseases which are caused by
Immunologists have identified many different types of
the immune system attacking the body are called
T-lymphocytes. Two of the most important is the T-
autoimmune diseases. Another profound similarity
helper lymphocytes (these are identified by the so-
between depression and autoimmune disease is the
called CD4 antigen on their cell surface) and the T-
very high incidence of depression with autoimmune
suppressor lymphocytes (these are identified by the
diseases.
so-called CD8 antigen on their cell surface) [24].
Typically, biomedical scientists either have no
Maes et al., in one of his many landmark
explanation for the high rates of depression occurring
papers on depression, reported extraordinarily
with autoimmune diseases or very convoluted
consistent evidence of T lymphocyte activation in
explanations. In sharp contrast, the immune-cytokine
depressed patients. Healthy controls were compared
model of depression has a clear and direct
to 101 depressed inpatients consecutively admitted to
explanation, i.e., the activated immune systems in
the Psychiatric Ward of the University Hospital of
persons with autoimmune disease secrete excessive
Antwerp. Depressed patients had significantly higher
amounts of cytokines. Excessive cytokines provoke
percentages of T-helper lymphocytes and lower
the symptoms and signs of depression [31].
percentages of T-suppressor lymphocytes than
healthy controls. The T-helper/T-suppressor ratio was Evidence suggests that these associations
significantly elevated in depressed patients. The can be affected by a) the clinical characteristics of
patients with the most severe depression had the depression (e.g., typical depression versus atypical
highest percentage of T-helper lymphocytes and the depression and exhaustion), b) the duration and
highest T-helper/T-suppressor ratio [28]. severity of depressive symptoms, and c) the stage of
an underlying CAD. Depressive symptoms are
A high percentage of T-helper lymphocytes
hypothesised to affect the transition primarily from
combined with the finding of monocytosis in
stable CAD to acute coronary syndromes via plaque
depression means that both the lymphocyte and the
activation and prothrombotic processes and may play
macrophage arms of the immune system are
an additional role in response to injury at early stages
activated. The reduced percentage of T-suppressor
of coronary atherosclerosis [24].
lymphocytes is another clear sign of the immune
system is energised. The high T-helper/T-suppressor Type D personality is a behavioural model in
ratio is a reliable indicator of immune system which people experience negative emotions such as
activation. In the same paper, Maes et al. provided depression, anger, hostility and anxiety while they
additional evidence of lymphocyte activation [28]. refuse to express it. Denolt (2000) identifies type D
personality in the long-term by an increased risk of the
Recently Müller et al. investigated the
first myocardial infarction [32]. Type D personality can
lymphocyte subsets of severely depressed patients.
lead to increased fatigue or depression among the
Their results were very similar to Maes et al. 's
people with such a personality type. Therefore, these
findings. Müller et al. 's paper provided independent
factors will be correlated with increase reactivity to
confirmation of over-active immune systems in
acute stresses [33].
severely depressed patients. Several earlier papers
by other scientists have also reported a high T- Type D personality is specified by a
helper/T suppressor ratio in depressed patients [29]. combination of two fixed personality structure:
negative affectivity and social inhibition [34][35].
Another reliable sign of lymphocyte activation
Negative affectivity is the tendency to experience
in the presence of interleukin2 receptors on the outer
negative emotions constantly such as restlessness,
surfaces of lymphocytes. Maes et al. reported that
boredom, fear and irritability in all times and
increased interleukin2 receptors on lymphocytes are a
situations. Social inhibition is the intendancy to inhibit
hallmark for major depression. This is further
expressing the emotions, high levels of insecurity
independent evidence of immune activation with
experience in social situations and extreme control of
depression [30].
self-revelation for fear of others’ displeasures [32].
The usual antibodies made by activated B- Type D personality is relatively common. The
lymphocytes will clump and identify foreign proteins. estimations show a range of 21-28% of cardiovascular
As soon as a foreign protein is tagged with an patients and 53% of the people with high blood
antibody, it will be devoured by macrophages and pressure among the public population [35] [36]. Type
killer lymphocytes. In this way, the immune system D personality theorists believe that the synergistic
can quickly identify and destroy foreign invaders. In effect of high negative affectivity and high social
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inhibition predict less health and especially poor and other medical disorders [54] [55]. Considerable
prognosis in the heart [34]. evidence suggests an association between
depression and hypertension, peptic ulcers, and
Previous studies indicate that type D
diabetes [54] [55]. Elevated cortisol may be a
personality predicts severe heart disease and it may
mediating factor in these relationships. Cortisol has
be associated with psychological and physiological
many effects that promote coronary heart disease. For
indicators of poor prognosis in patients with heart
example, cortisol inhibits the growth hormone and
disease [37] [38]. Type D personality is parallel to
gonadal axes. Growth hormone deficiency is
psychological distress in patients with CHD including
associated with a higher relative risk for premature
signs of social alienation, depression, anger, anxiety,
cardiovascular disease in adults [56] [57]. Cortisol is a
paranoia and vital exhaustion [39]. The patients with
potent stimulus to visceral fat. Inhibition of the growth
type D are more likely to commit maladaptive health
hormone and gonadal axes exacerbates visceral fat
behaviours such as smoking and a poor diet. The
accumulation. Excess visceral fat leads to
people with type D personality use the solutions for
dyslipidaemia and, along with hypercortisolism, to
dysfunctional coping strategies in response to disease
insulin resistance, hyperinsulinism, and their sequelae
[40]. Therefore, type D personality can lead to a
[58]. Similar mechanisms may increase the
poorer prognosis by affecting the selection of lifestyles
vulnerability of type D individuals to cardiac and other
among the patients with CVD [41]. Also, the studies
medical illnesses. Elevated cortisol may be a
show the relationship between anger (as one of the
mediating factor in the association between type D
negative affectivity components in type D personality)
personality and the increased risk for coronary heart
and the increased cardiovascular diseases [42] [43].
disease and, possibly, other medical disorders. It is
Type D individuals tend to experience important to note that cortisol is not the only mediating
negative emotions such as depressed mood, anxiety, factor in this association. A recent study suggests that
anger, hostile feelings, and to inhibit these emotions type D personality is associated with increased
while avoiding social contacts [44] [45] [46]. Situations circulating levels of cytokine tumour necrosis factor α
involving fear, anxiety, helplessness, and loss of and its soluble receptors 1 and 2, which are predictors
control result in the release of cortisol [47] [48]. The of mortality in chronic heart failure [59].
relationship between negative affect and cortisol
Depression is associated with impairment in
activity has been documented in several studies using
feedback control of the HPA axis, contributing to
structured laboratory stressors, such as public
higher cortisol levels during episodes of depression
speaking and mental arithmetic [49] and aversive
[50] [60]. Prolonged exposure to elevated cortisol
stimulation [48], and in the scientific literature related
levels may be neurotoxic, especially for brain regions
to changes in the hypothalamic-pituitary-adrenal
rich in corticosteroid receptors, and may mediate
(HPA) axis in depressed patients [50] [51]. A recent
neuronal vulnerability to stressors. Recurrent
study has documented relationships between negative
depression is associated with atrophy of the
affect, positive affect and cortisol in response to
hippocampus and amygdala [61] [62] as well as the
naturalistic stressors [52]. Both the experience of a
prefrontal cortex [63]. A gradual deterioration of
current stressor and anticipating a stressor were
hippocampal feedback inhibition of the HPA axis due
associated with increased salivary cortisol levels.
to down-regulation of glucocorticoid receptors from
Negative affect was associated with higher cortisol
repeated stress has been demonstrated [64]
levels, and positive affect was associated with lower
[65]. Evidence suggests that age and/or length of
cortisol levels. Another study also found that stressful
depression and/or the number of depressive episodes
daily events were associated with increased cortisol
affect HPA regulation in depressed patients [51] [61]
secretion in healthy volunteers [53]. Distress, as
[62]. The potentiating or additive effect of age in
reflected by the mood states ‘negative affect’ and
conjunction with depression on pituitary-adrenocortical
‘agitation’, was associated with higher cortisol levels.
activity was suggested by some studies [51] [62]
Mood plays a mediating role in the relationship
[67]. Mean 24-h cortisol level increases with age in
between stressful events and cortisol secretion [52]
depression [68]. Elderly depressives who are cortisol
[53]. Negative affectivity is not just a confounder but is
non-suppressors after dexamethasone need more
related to elevated cortisol secretion during normal
time for pituitary adrenocortical normalisation to occur
daily activities. In a recent study, both type D
than do younger subjects [69]. An increase in post-
dimensions (negative affectivity and social inhibition)
dexamethasone cortisol levels with age has been
were associated with greater cortisol reactivity to
reported in major depressive disorder [70]. A
stress [46], although the results were not significant in
significant effect of age on cortisol release in
more stringent regression analyses. However, it is
depressed patients has been observed during the
reasonable to suggest that there is a difference in
combined dexamethasone-corticotropin-releasing
HPA regulation in type D individuals and people with
hormone test: older patients had higher post-
other personality types.
dexamethasone cortisol levels [71]. In patients with
Depression appears to be an independent risk endogenous depression, advancing age leads to
factor for the development of coronary heart disease higher baseline cortisol and a greater likelihood of
and osteoporosis and affects the prognosis of these being a dexamethasone non-suppressor [72]. Cortisol
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responses to fenfluramine administration in depressed Chemokine clusters [85]. They also confirm the
patients increased with the number of major relationship between hostility and increased
depressive episodes [51]. Other authors have proinflammatory and anti-inflammatory cytokines [85].
reported similar observations [66] [68] [73]. However, Bacon et al., (2006) address that mental stress leads
some authors suggest that age does affect HPA to heart pain and myocardial ischemia among the
regulation in healthy humans [74] [75]. Differences in patients with cardiovascular patients [86]. Decreased
the results of studies have been be explained by plasma volume may be a mechanism by which
differences in a sample size, screening criteria, and potential mental stress is increased for acute
some other factors, such as differences in sleeping cardiovascular events [87]. Bosch et al., (2003) also
patterns [51] [76]. show that acute stress causes to move T cells which
were initially induced for response to inflamed
Equivocal results of these studies may be, in
endothelium [81]. Acute stressors can help to absorb
part, related to a different prevalence of type D
circulation of immune cells under endothelium and
individuals in study samples: i.e. some type D
hence to accelerate plaque formation and lead to the
individuals may have alterations within the HPA axis
effects caused by acute stressors. This mechanism
that are similar to HPA axis changes in depressed
can help to express the relationship between stress
patients [77]. Future studies of HPA function should
and cardiovascular diseases [88].
control for the presence of type D individuals. Type D
individuals should perhaps not participate in Also, the depression risk factor is addressed
psychobiological studies as healthy controls. Studies by plenty of researchers. Masselman and Freedland
of HPA function should also control for other (2002) show biological processes associated with the
personality traits that may affect the HPA axis. For role of depression on CHD risk in women [89]. They
example, individuals with borderline or antisocial conclude that the depression causes to increase
personality features may have HPA axis abnormalities blood pressure and also elevate the risk of coronary
[78] [79] [80]. arteries occlusion by platelet aggregation and
accumulation of steroid hormones [89]. Ladwig et al.,
(2003) and Miller et al., (2003) show both the
relationship between depressive disorders and
inflammation markers as well as significant relations
Results among the people with overweight [90] [91]. Miller et
al., (2003) use Structural Equation Modeling to
determine the role of leptin regarding depression,
To clarify the discussion, it is necessary to obesity and CRP and IL-6 markers. Von Kanel et al.,
have a glance at some studies associated with (2008) indicate that depression signs-as one of the
psychological risk factors including depression, stress cardiovascular diseases risked factors-predict
and type D personality on CAD. The stress is also increases TNF-α level and decreased IL-4 as well as
addressed by plenty of researchers. Lots of studies the elevated ratio of IL-4 to TNF-α [92]. Ranjit et al.,
report changes in quantity and ratio of T and B cell as (2007) show, in a study on psychosocial risk factors
well as changes in Natural Killer (NK) Cells and for cardiovascular disease, the positive relationship
cykotines and failure in functional responses due to between severity of depression and an increase of IL-
acute psychological stresses. Nevertheless, recent 6 level [93]. Personality type risk factor is also studied
studies often focus on the relationship between street in several papers. Denollet et al., (2003) address type
with other psychological factors and inflammatory D personality for chronic negative affectivities and
markers [34]. present some evidence on increased TNF-α among
Bosch et al. (2003) show a considerable the patients with congenital heart failure having type D
amount of Chemokine receptor incidence by T cells compared to those without type D [94]. Gridon et al.,
caused by induced stress [81]. Mills et al., (1995) (2003) investigate the conventional chemical indices
show that immune responses caused by stress are among the admitted patients without acute coronary
strengthened among the people with high blood syndromes and observe that chronic psychological
pressure [82]. Besides, Fuligni et al., (2009) show an risk factors are associated with increased white blood
increased CRP level due to increased experience of cell count and lymphocyte percentage [95]. Pedersen
daily stresses, considering CRP as one of the and Middel (2001) recognised type D personality
inflammatory indices for cardiovascular diseases [83]. independent of such factors as disease severity and
Benson et al., indicate that acute stress leads to a argue it causes to increase the risk of bad prognosis
significant increase of CRP and IL-6 in fat women up to 2-5 times, decrease life quality and arise factors
[84]. Steptoe et al. (2007) conclude, in a review study of stress and depression [96].
on interface mechanisms between psychological Although there exists low information about
factors and cardiovascular diseases risk that IL-1 and harmful impacts of type D personality in clinical
IL-6 increase after acute stress [9]. results, these can be some possible causes: immune
Also, Mommersteeg et al., (2008) indicate the system, the behaviours associated with health
relationship between hostility and Cytokine/ including smoking and refusal of medical commands.
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Pederson et al., (2004) the study impact of type D physiologic and pathologic changes of myocytes in
personality on the occurrence of side effects among the adult human’s heart has presented the
the patients with Ischaemic Heart Disease (IHD) after fundamental base of regeneration therapy. Different
Percutaneous Coronary Intervention (PCI) by methods have been represented experimentally in this
Sirolimus-Eluting Stent (SESs) or Bare Metal Stent regard among which some selected cases were used.
(BMSs) for nine months [97]. Regardless of the stent This history starts with skeletal myoblasts and bone
type, the patients with type D personality are more marrow-derived cells and then proceeds already with
likely to be on the subject of death and MI compared stem/Mesenchymal stromal cells inside the heart.
to those without type D personality for nine months Among them, C-KIT (positive) cardiac stem cell
[97]. The patients with depression or type D transplantation caused leading results with long-term
personality are in the subject of the risk of improper impacts without side effects in the patients with
response to treatment by the stent. The patients with chronic ventricular dysfunction. For more optimisation
type D personality often expect unsuitable clinical of present methods, we should identify different
consequences in IHD along with Left ventricular factors including the target disease, cellular population
dysfunction [97]. and quantity of injected cells as well as cell transfer
method. Identification of former clinical tests results
Also, some studies focus on stem cells.
allows us to predict an ideal cell therapy for different
Recent studies in this regard have expanded our
cardiovascular disorders [100].
knowledge on Haematopoietic Stem Cell (HSC)
niches which are important to maintain and conduct
renewal and differentiation the HSC. Osteoblasts,
Mesenchymal Stem Cells (MSCs) and CXCL12-
Abundant Reticular (CAR) cells are components of the Discussion
bone marrow microenvironment and are associated
with HSCs which are specified in the performance of
body immune system and Homeostasis. It is The connection between heart and mind is a
noteworthy to say that cell populations of the bone deep and prolonged bond. Advances in modern
marrow microenvironment send a message for behavioural medicine have shifted psychology
different and proper functions of the immune system specialists towards the key role of abiotic factors in
through G Protein-Coupled Receptors (GPCRs) [98]. CHD. The researches on this disease have paid
MI is the main mortality cause in industrial psychological factors into attention for a while, and the
countries. Therefore, stem cells-based therapeutical relationship between immune system parameters and
approaches are an important necessity for MI in psychological factors is an important topic of today
Regenerative Medicine and coronary arteries. The studies on the progression of a CAD. In this regard,
experimental studies show that stem cells derived the present study aimed to investigate the effect of
from Bone marrow endothelial progenitor cells can three psychological factors including depression,
improve the coronary performance after Myocardial stress, and Type D personality on the immune system
Infarction. Phases I and II studies started quickly to in coronary artery disease. Generally, the research
transfer these concepts to the clinical stage. However, findings discussed in this review confirm the validity of
impacts of stem/ progenitor cells on MI in a clinical the hypothesis that psychoneuroimmunologic
stage have not met the expectations so far. Therefore, processes involved cardiovascular diseases. A set of
a better understanding of the common limitation these findings which have been published earlier are
causes is necessary for cell therapy approaches. It is based on hypotheses about the potential role of
again noteworthy to mention that quantity and psychoneuroimmunologic pathways in the
performance of endothelial progenitor cells is pathogenesis of cardiovascular diseases.
decreased among the patients with cardiovascular risk Figure 2 which is derived from Kop’s theory
factors or CAD. These observations may provide the shows three categories of psychological factors
opportunities to optimise and amend cell therapy (acute, episodic and chronic), immune system
approaches. In present review study, a summary of parameters related to CAD progression and
current evidence on the role of stem/progenitor cells in progression stages of heart diseases and pathologic
pathophysiology and treatment of ischemic diseases changes/lesions in coronary arteries, respectively
is presented including properties of the cells, from left to right [7]. As it can be seen at the right edge
regeneration capacity in the colony of stem/progenitor of the figure, the initial stages of coronary
cells. Also, stem/progenitor cells delivery methods, arteriosclerosis are specified by monocytes deposition
their implantation adjustment as well as potential in arteries wall that in this process, adhesion
approaches to start employment of stem/ progenitor molecules play an important role. In the next stages of
cells in cell therapy methods are explained for CAD, cytokines involved in the activation of T cells
cardiovascular diseases [99]. and the formation of macrophage foam cells. In this
While the requests are increasing stage, the performance of Endothelial will diminish
considerably for effective therapeutic choices for and thereby its dilation, and contractile properties will
chronic coronary failure, the recent identification of be lowered to respond to blood flow and other arteries
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vasodilatation stimuli. these factors and CAD severity [103]. Therefore, the
processes involved in atherosclerotic plaques
After initial vascular lesions, Smooth muscle
transition from stable to unstable mode are the
cells will proliferate and migrate to plaque surface and
probable factors which contribute on the formation of
finally contribute to form a fibrous coating with a stable
predictor role for depression and other episodic
ration on atherosclerotic lesions. In severe CAD
factors in acute coronary syndromes [1] [6] [106].
mode, several factors may cause to stimulate the
Immunologic correlates of depression include
plaque and result in lesion instability and thinning of
increased leukocytes of peripheral blood (mainly
the fibrous coating. The plaque rupture leads to partial
neutrophils and monocytes), decreased lymphocyte
or complete occlusion of coronary arteries. This lesion
count, elevated serum cytokines (IL-6 and TNF-α),
often is caused by thrombus formation resulting from
reduced indices of cell function and increased viral
blood contact with collagen. Sudden occlusion of
antibodies (e.g. cytomegalovirus) [7] [106].
coronary arteries can cause cardiac ischemia and
chest pain while complete and continuous clotting Stable conditions such as type D personality
results in myocardial infarction [101] [102]. More are related to increased risk of first myocardial
precise studies on this complex process can be infarction in a long-term period [107]. Pro-atherogenic
followed up in several types of research. processes-which cause to increase lipid deposition
Psychological risk factors are effective through and inflammatory processes due to the sympathetic
differentiated immunologic processes in the nervous system-are of the well-known
pathophysiological trend of heart. pathophysiologic pathways among chronic risk factors
and initial stages of CAD [7]. Also, chronic
Pathophysiologic mechanisms involved in
psychological factors involved in the appearance of
stress include Catecholamines increase due to the
episodic risk factors. For instance, these factors can
sympathetic nervous system, increased heart rate and
be associated with an increased incidence of
blood pressure, decreased plasma volume and
depression or exhaustion [104]. Therefore, the
coronary vasoconstriction [86]. Immune system
prediction power of chronic psychological factors is
responses to stress can potentially help
somewhat influenced by their relation with episodic
Atherosclerotic plaque rupture. Most of the studies on
and acute [sychological risk factors for CAD. Kop
psycho-immunology show increased CD8+ cells and
refers to Jeron et al., in which neurohormones are
decreased CD4+ cells, as well as increased blood
proved as the potential factors for cytokine myocardial
viscosity and stimulating the immune system in
(IL-6) adjustment using an experimental model [7].
response to acute psychological challenges [7] [9].
These responses are the same as acute phase Regarding the mechanism of type D
reactivity and relate to Hemodynamic responses to personality components effectiveness on coronary
acute stresses [1]. arteries narrow, the effects they make on the coronary
system can be referred. Negative affectivity causes to
increase Cortisol levels. Therefore, the people who
experience negative affectivities are more prone to
increased blood pressure and heart failure. In other
words, stress hormones like Cortisol may be adjusted
unsuitably among the patients with type D personality
[43] [108]. This leads to increase blood pressure and
blood vessel blockages. The arteries occlusion does
not allow the blood full of oxygen to reach sufficiently
the heart. On the other hand, the patients with type D
personality may have a more active immune system
with more inflammation which may damage blood
vessels.
Figure 2: Acute, episodic and chronic psychological risk factors Briefly, the present study aimed to describe
model by the immune system parameters involved in Coronary
Arteries Disease
psychoneuroimmunological processes which
contribute to CAD and CHD progression. Such
psychological risk factors as stress, depression and
The value of depression- as the predictor type D personality were investigated here.
variable for unsuitable long-term cardiac Psychoneuroimmunological pathways of all three
consequences- relates to its relapsing nature [1] [103]. mentioned risk factors were described for CAD. The
In major depression, secretion of Corticotropin- studies review indicated that stress could be
Releasing Hormone (CRH) and repeated activation of accompanied with myocardial ischemia and help to
HPA axis and thereby irregularity in this axis are seen rupture. The depression involves in the transfer of
[103] [104] [105]. Since psychological risk factors of stable atherosclerotic plaque to unstable, and type D
depression have temporary nature. In most of the personality is effective on initial stages of a CAD.
studies, no significant correlation is found between However, most of the statistical indices in this
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