Search Results (22)

Vulnerable atherosclerotic plaques, especially hemorrhaged lesions, are the major cause of mortalities related to vascular pathologies. The early identification of vulnerable plaques helps to stratify patients at risk of developing acute vascular events. In this study, proteomics analyses of human carotid artery samples collected from patients with atheromatous plaques and complicated lesions, respectively, as well as from healthy controls were performed. The proteins isolated from the carotid artery samples were analyzed by a bottom-up shotgun approach that relied on nanoflow liquid chromatography–tandem mass spectrometry analyses (LC–MS/MS) using both data-dependent (DDA) and data-independent (DIA) acquisitions. The data obtained by high-resolution DIA analyses displayed a stronger distinction among groups compared to DDA analyses. Differentially expressed proteins were further examined using Ingenuity Pathway Analysis^® with focus on pathological and molecular processes driving atherosclerosis. From the more than 150 significantly regulated canonical pathways, atherosclerosis signaling and neutrophil extracellular trap signaling were verified by protein-targeted data extraction. The results of our study are expected to facilitate a better understanding of the disease progression’s molecular drivers and provide inspiration for further multiomics and hypothesis-driven studies. Full article

Atherosclerosis, a term derived from the Greek “athero” (atheroma) and “sclerosis” (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice. Full article

Atherosclerosis (AS) is a severe vascular disease that results in millions of cases of mortality each year. The development of atherosclerosis is associated with vascular structural lesions, characterized by the accumulation of immune cells, mesenchymal cells, lipids, and an extracellular matrix at the intimal resulting in the formation of an atheromatous plaque. AS involves complex interactions among various cell types, including macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs). Endothelial dysfunction plays an essential role in the initiation and progression of AS. Endothelial dysfunction can encompass a constellation of various non-adaptive dynamic alterations of biology and function, termed “endothelial reprogramming”. This phenomenon involves transitioning from a quiescent, anti-inflammatory state to a pro-inflammatory and proatherogenic state and alterations in endothelial cell identity, such as endothelial to mesenchymal transition (EndMT) and endothelial-to-immune cell-like transition (EndIT). Targeting these processes to restore endothelial balance and prevent cell identity shifts, alongside modulating epigenetic factors, can attenuate atherosclerosis progression. In the present review, we discuss the role of endothelial cells in AS and summarize studies in endothelial reprogramming associated with the pathogenesis of AS. Full article

Computed tomography angiography (CTA) has validated the use of pericoronary adipose tissue (PCAT) attenuation as a credible indicator of coronary inflammation, playing a crucial role in coronary artery disease (CAD). This study aimed to evaluate the long-term effects of high-dose statins on PCAT attenuation at coronary lesion sites and changes in plaque distribution. Our prospective observational study included 52 patients (mean age 60.43) with chest pain, a low-to-intermediate likelihood of CAD, who had documented atheromatous plaque through CTA, performed approximately 1 year and 3 years after inclusion. We utilized the advanced features of the CaRi-Heart^® and syngo.via Frontier^® systems to assess coronary plaques and changes in PCAT attenuation. The investigation of changes in plaque morphology revealed significant alterations. Notably, in mixed plaques, calcified portions increased (p < 0.0001), while non-calcified plaque volume (NCPV) decreased (p = 0.0209). PCAT attenuation generally decreased after one year and remained low, indicating reduced inflammation in the following arteries: left anterior descending artery (LAD) (p = 0.0142), left circumflex artery (LCX) (p = 0.0513), and right coronary artery (RCA) (p = 0.1249). The CaRi-Heart^® risk also decreased significantly (p = 0.0041). Linear regression analysis demonstrated a correlation between increased PCAT attenuation and higher volumes of NCPV (p < 0.0001, r = 0.3032) and lipid-rich plaque volume (p < 0.0001, r = 0.3281). Our study provides evidence that high-dose statin therapy significantly reduces CAD risk factors, inflammation, and plaque vulnerability, as evidenced by the notable decrease in PCAT attenuation, a critical indicator of plaque progression. Full article

Background: Atherosclerosis is a progressive disease that results from endothelial dysfunction, inflammatory arterial wall disorder and the formation of the atheromatous plaque. This results in carotid artery stenosis and is responsible for atherothrombotic stroke and ischemic injury. Low-grade plaque inflammation determines biological stability and lesion progression. Methods: Sixty-seven cases with active perilesional inflammatory cell infiltrate were selected from a larger cohort of patients undergoing carotid endarterectomy. CD68+, iNOS2+ and Arg1+ macrophages and CD31+ endothelial cells were quantified around the atheroma lipid core using digital morphometry, and expression levels were correlated with determinants of instability: ulceration, thrombosis, plaque hemorrhage, calcification patterns and neovessel formation. Results: Patients with intraplaque hemorrhage had greater CD68+ macrophage infiltration (p = 0.003). In 12 cases where iNOS2 predominated over Arg1 positivity, the occurrence of atherothrombotic events was significantly more frequent (p = 0.046). CD31 expression, representing neovessel formation, correlated positively with atherothrombosis (p = 0.020). Conclusions: Intraplaque hemorrhage is often described against the background of an intense inflammatory cell infiltrate. Atherothrombosis is associated with the presence of neovessels and pro-inflammatory macrophages expressing iNOS2. Modulating macrophage polarization may be a successful therapeutic approach to prevent plaque destabilization. Full article

A warning sign for impending cardiovascular events is not fully established. In the process of plaque rupture, the formation of vulnerable plaque is important, and oxidized cholesterols play an important role in its progression. Furthermore, the significance of vasa vasorum penetrating the medial smooth muscle layer and being rich in atheromatous lesions should be noted. The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. The CAVI reflects functional stiffness, in addition to structural stiffness. The rapid rise in the CAVI means medial smooth muscle cell contraction and strangling vasa vasorum. A rapid rise in the CAVI in people after a big earthquake, following a high frequency of cardiovascular events has been reported. There are several cases that showed a rapid rise in the CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis: a rapid rise in the CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading to ischemia and the necrosis of vulnerable plaque, and then the plaque ruptures. In individuals having a high CAVI, further rapid rise in the CAVI might be a warning sign for impending cardiovascular events. In such cases, treatments to decrease the CAVI better be taken soon. Full article

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterious and venous thrombosis, miscarriage, and the presence of antiphospholipid antibodies (aPL) in the blood. As we know, APS is also characterised by accelerated atherosclerotic degeneration with an increased risk of thrombosis in all blood vessels, including the carotid arteries. Carotid artery stenosis can manifest in many different ways. The aim of this study is to present the results of our multidetector computerised tomography angiography (MDCTA) analysis of the carotid arteries in patients with primary and secondary APS compared with a control group. Materials and Methods: This study examined 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with secondary antiphospholipid syndrome (SAPS). The results were compared with a control group also comprising 50 patients. The groups were analysed with respect to age, sex and the presence of well-established risk factors for vascular disease. The study was conducted using MDCTA, where we analysed the quantitative and qualitative (morphologic) characteristics of carotid artery lesions. Results: Patients from the control group had significantly elevated levels of cholesterol and triglycerides in comparison with patients with PAPS and SAPS (p < 0.001 and p < 0.05). The results show that carotid artery lesions were significantly more common in patients with APS (PAPS, n = 40, CI95: 0.50–0.75, p = 0.0322 and SAFS, n = 54, CI95: 0.59–0.80, p = 0.0004) than within the control group (n = 23). There was a statistically significant difference between patients with APS and the control group with respect to lesions in the distal segments (n = 27, CI95: 0.67–0.95, p = 0.0001), bulbi and proximal segments (n = 21, CI95: 0.84–1.00, p = 0.000005). The number of patients with one lesion (L) (n = 27) was significantly greater than the number of those with three (n = 10, CI95: 0.56–0.86, p = 0.0051) or four (n = 3, CI95: 0.73–0.98, p = 0.00001) lesions. There were also more patients with two lesions (n = 24) than those with four (n = 3) (CI95: 0.71–0.97, p = 0.00005). Carotid artery stenosis was shown as a percentage of the carotid artery lumen diameter (%DS). Stenosis of up to 30%, was more common in patients in the PAPS group (n = 12) than in the control group (n = 3) (CI95: 0.52–0.96, p = 0.0201), while the SAPS group (n = 17) had an even larger disparity (CI95: 0.62–0.97, p = 0.0017). We observed a highly significant difference in the frequency of stenoses between 30% and 50% DS between the PAPS group (n = 24) and the control group (n = 7) (CI95: 0.59–0.90, p = 0.0023), as well as the SAPS group (n = 30) (CI95: 0.65–0.92, p = 0.0002). A qualitative analysis of plaque morphology revealed that patients with PAPS had significantly more soft tissue lesions (n = 23) compared with calcified lesions (n = 2) (CI95: 0.74–0.99, p = 0.00003), as well as more mixed plaques (n = 9) and calcified plaques (n = 2) (CI95: 0.48–0.98, p = 0.0348). Patients within the SAPS group had significantly more soft tissue (n = 35) than calcified lesions (n = 3) (CI95: 0.79–0.98, p = 0.00000021), as well as more mixed lesions (n = 21) compared with calcified (n = 3) (CI95: 0.68–0.97, p = 0.0002). Conclusions: Our study shows that subclinical manifestations of carotid artery lesions were more common in patients with APS. We came to the conclusion that MDCTA is an accurate diagnostic method because it is a safe method that provides us with a great quantity of accurate information about the characteristics of atheromatous plaques, which aids us in the further planning of treatment for patients with APS. Full article

There are a number of devastating complications associated with peripheral artery disease, including limb amputations and acute limb ischemia. Despite the overlap, atherosclerotic diseases have distinct causes that need to be differentiated and managed appropriately. In coronary atherosclerosis, thrombosis is often precipitated by rupture or erosion of fibrous caps around atheromatous plaques, which leads to acute coronary syndrome. Regardless of the extent of atherosclerosis, peripheral artery disease manifests itself as thrombosis. Two-thirds of patients with acute limb ischemia have thrombi associated with insignificant atherosclerosis. A local thrombogenic or remotely embolic basis of critical limb ischemia may be explained by obliterative thrombi in peripheral arteries of patients without coronary artery-like lesions. Studies showed that thrombosis of the above-knee arteries was more commonly due to calcified nodules, which are the least common cause of luminal thrombosis associated with acute coronary events in patients with acute coronary syndrome. Cardiovascular mortality was higher in peripheral artery disease without myocardial infarction/stroke than in myocardial infarction/stroke without peripheral artery disease. The aim of this paper is to gather published data regarding the disparities of acute coronary syndrome with and without peripheral artery disease in terms of pathophysiology and mortality. Full article

Backgrounds: One of the major hypotheses for early neurological deterioration (END) in single small subcortical infarction (SSSI) is the process of atherosclerosis. However, the association between statin therapy, especially high-intensity statin therapy, and its effectiveness in reducing the incidence of END during the acute phase of SSSI remains unclear. This study aimed to investigate the influence of high-intensity statin therapy compared to moderate-intensity statin therapy during the acute phase on the incidence of END in SSSI. Methods: The records of 492 patients with SSSI who received statin therapy within 72 h of symptom onset from a prospective stroke registry were analyzed. The association between END and statin intensity was evaluated using multivariable regression analysis for adjusted odds ratio (aOR). Results: Of the 492 patients with SSSI (mean age: 67.2 years, median NIHSS score on admission: 3), END occurred in 102 (20.7%). Older age (aOR, 1.02; 95% confidence interval (CI), 1.00–1.05; p = 0.017), and branch atheromatous lesion (aOR, 3.49; 95% CI 2.16–5.74; p < 0.001) were associated with END. Early high-intensity statin therapy was associated with a lower incidence of END than moderate-intensity statin therapy (aOR, 0.44; 95% CI, 0.25–0.77; p = 0.004). In addition, there was significantly lower incidence of END in early administration (≤24 h) of high-intensity statin group. Conclusions: We identified an association between the intensity of early statin therapy and END in patients with SSSI. Early administration of high-intensity statin (≤24 h) is associated with a reduced incidence of END in patients with SSSI. Full article

SMTP-44D has been reported to have anti-oxidative and anti-inflammatory reactions, including reduced expression of receptor for advanced glycation end products (RAGE) in experimental diabetic neuropathy. Although activation of RAGE with its ligands, and advanced glycation end products (AGEs), play a crucial role in atherosclerotic cardiovascular disease, a leading cause of death in diabetic patients, it remains unclear whether SMTP-44D could inhibit experimental atherosclerosis by suppressing the AGEs–RAGE axis. In this study, we investigated the effects of SMTP-44D on atherosclerotic plaque formation and expression of AGEs in apolipoprotein-E null (Apoe^−/−) mice. We further studied here whether and how SMTP-44D inhibited foam cell formation of macrophages isolated from Apoe^−/− mice ex vivo. Although administration of SMTP-44D to Apoe^−/− mice did not affect clinical or biochemical parameters, it significantly decreased the surface area of atherosclerotic lesions and reduced the atheromatous plaque size, macrophage infiltration, and AGEs accumulation in the aortic roots. SMTP-44D bound to immobilized RAGE and subsequently attenuated the interaction of AGEs with RAGE in vitro. Furthermore, foam cell formation evaluated by Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and gene expression of RAGE, cyclin-dependent kinase 5 (Cdk5) and CD36 in macrophages isolated from SMTP-44D-treated Apoe^−/− mice were significantly decreased compared with those from saline-treated mice. Gene expression levels of RAGE and Cdk5 were highly correlated with each other, the latter of which was also positively associated with that of CD36. The present study suggests that SMTP-44D may inhibit atherosclerotic plaque formation in Apoe^−/− mice partly by blocking the AGEs-RAGE-induced ox-LDL uptake into macrophages via the suppression of Cdk5-CD36 pathway. Full article

During the COVID-19 pandemic induced by the SARS-CoV-2, numerous chest scans were carried out in order to establish the diagnosis, quantify the extension of lesions but also identify the occurrence of potential pulmonary embolisms. In this perspective, the performed chest scans provided a varied database for a retrospective analysis of non-COVID-19 chest pathologies discovered de novo. The fortuitous discovery of de novo non-COVID-19 lesions was generally not detected by the automated systems for COVID-19 pneumonia developed in parallel during the pandemic and was thus identified on chest CT by the radiologist. The objective is to use the study of the occurrence of non-COVID-19-related chest abnormalities (known and unknown) in a large cohort of patients having suffered from confirmed COVID-19 infection and statistically correlate the clinical data and the occurrence of these abnormalities in order to assess the potential of increased early detection of lesions/alterations. This study was performed on a group of 362 COVID-19-positive patients who were prescribed a CT scan in order to diagnose and predict COVID-19-associated lung disease. Statistical analysis using mean, standard deviation (SD) or median and interquartile range (IQR), logistic regression models and linear regression models were used for data analysis. Results were considered significant at the 5% critical level (p < 0.05). These de novo non-COVID-19 thoracic lesions detected on chest CT showed a significant prevalence in cardiovascular pathologies, with calcifying atheromatous anomalies approaching nearly 35.4% in patients over 65 years of age. The detection of non-COVID-19 pathologies was mostly already known, except for suspicious nodule, thyroid goiter and the ascending thoracic aortic aneurysm. The presence of vertebral compression or signs of pulmonary fibrosis has shown a significant impact on inpatient length of stay. The characteristics of the patients in this sample, both from a demographic and a tomodensitometric point of view on non-COVID-19 pathologies, influenced the length of hospital stay as well as the risk of intra-hospital death. This retrospective study showed that the potential importance of the detection of these non-COVID-19 lesions by the radiologist was essential in the management and the intra-hospital course of the patients. Full article

Atherosclerosis is a chronic inflammatory arterial disease characterized by build-up of atheromatous plaque, which narrows the lumen of arteries. Hypercholesterolemia and excessive oxidative stress in arterial walls are among the main causative factors of atherosclerosis. Transient receptor potential channel M2 (TRPM2) is a Ca²⁺-permeable cation channel activated by oxidative stress. However, the role of TRPM2 in atherosclerosis in animal models is not well studied. In the present study, with the use of adeno-associated virus (AAV)-PCSK9 and TRPM2 knockout (TRPM2^−/−) mice, we determined the role of TRPM2 in hypercholesterolemia-induced atherosclerosis. Our results demonstrated that TRPM2 knockout reduced atherosclerotic plaque area in analysis of En face Oil Red O staining of both whole aortas and aortic-root thin sections. Furthermore, TRPM2 knockout reduced the expression of CD68, α-SMA, and PCNA in the plaque region, suggesting a role of TRPM2 in promoting macrophage infiltration and smooth-muscle cell migration into the lesion area. Moreover, TRPM2 knockout reduced the expression of ICAM-1, MCP-1, and TNFα and decreased the ROS level in the plaque region, suggesting a role of TRPM2 in enhancing monocyte adhesion and promoting vascular inflammation. In bone-marrow-derived macrophages and primary cultured arterial endothelial cells, TRPM2 knockout reduced the production of inflammatory cytokines/factors and decreased ROS production. In addition, a TRPM2 antagonist N-(p-amylcinnamoyl) anthranilic acid (ACA) was able to inhibit atherosclerotic development in an ApoE^−/− mouse model of atherosclerosis. Taken together, the findings of our study demonstrated that TRPM2 contributes to the progression of hypercholesterolemia-induced atherosclerosis. Mechanistically, TRPM2 channels may provide an essential link that can connect ROS to Ca²⁺ and inflammation, consequently promoting atherosclerotic progression. Full article

Although pontine infarction is the most common subtype of posterior circulation stroke, there has been little research focusing on recurrent pontine infarction. Our study aimed to investigate the factors associated with site and mechanism of recurrent pontine infarction. Patients with acute isolated pontine infarction were enrolled and followed up for one year. Lesion topography was determined by diffusion-weighted imaging. Mechanisms were determined based on lesion topography and other vascular, cardiologic and laboratory results. A total of 562 patients with pontine infarction were included, with 67 patients experiencing recurrence during the follow-up period. Forty-one recurrences occurred at the same site as index pontine infarction (41/67, 61.2%). Results indicated that the mechanism of index pontine infarction was significantly associated with the recurrent sites (p = 0.041, OR 2.938, 95% CI 1.044–8.268), and also with the mechanisms of recurrence (p = 0.004, OR 6.056, 95% CI 1.774–20.679). Branch atheromatous disease-induced index pontine infarction was likely to recur at the same site and with the same mechanism. Moreover, if recurrence occurred at the same site, the mechanism was probably the same as that of the index stroke (p = 0.000). Our study may help physicians treat patients with pontine infarction by predicting the site and mechanism of recurrence. Full article

Endarterectomy is an effective intervention to remove the atheromatous plaque in the inner lining of the artery, aiming to revascularize the occluded/stenosed vessel in patients with peripheral arterial occlusive disease (PAOD). The most common wound-related complication is postoperative bleeding, followed by infection, hematoma, and seroma. However, hematoma complications with air surrounded have rarely been reported in clinical cases. Case presentation: A 90-year-old female patient visited our emergency department because of a rapidly growing hematoma with pulsatile bleeding over her right groin area. She had received bilateral percutaneous transluminal angioplasty with endarterectomy for PAOD one month prior. A point-of-care ultrasound revealed a large hypoechoic mass, with a dirty shadow on the right groin area. Computed tomography angiography showed a hematoma over her right femoral region, with free air surrounding the right femoral artery. Angiography revealed an irregular shaped lesion on the right femoral artery without contrast extravasation. The patient was diagnosed with right-femoral post-endarterectomy infection with infected hematoma, with the inclusion of air. She underwent urgent excision and repair of the right femoral artery infectious lesion, debridement of the infectious hematoma and stenting of the right external iliac artery, common femoral artery and superficial femoral artery. Full article

Spinal anesthesia is generally accepted as an effective and safe practice. Three rare incidents of postoperative cerebral infarction after surgery under spinal anesthesia prompted us to assess whether spinal bupivacaine may compromise carotid or cerebral blood flow. Postoperative examination after the stroke incident revealed that all three patients shared a common pathology of stenosis or atheromatosis in the carotid or middle cerebral artery. In a companion study using 69 Sprague-Dawley rats, subarachnoid application of bupivacaine elicited an initial (Phase I) reduction in the mean arterial pressure, carotid blood flow (CBF) and baroreflex-mediated sympathetic vasomotor tone, all of which subsequently returned to baseline (Phase II). Whereas heart rate (HR) exhibited sustained reduction, cardiac vagal baroreflex, baroreflex efficiency index (BEI) and tissue perfusion and oxygen in the cerebral cortex remained unaltered. However, in one-third of the rats studied, Phase II gave way to Phase III characterized by secondary hypotension and depressed baroreflex-mediated sympathetic vasomotor tone, along with declined HR, sustained cardiac vagal baroreflex, decreased BEI, reduced CBF and waning tissue perfusion or oxygen in the cerebral cortex. We concluded that carotid and cerebral blood flow can indeed be compromised after spinal anesthesia, and an impaired baroreflex-mediated sympathetic vasomotor tone, which leads to hypotension, plays a contributory role. Full article