Nothing Special   »   [go: up one dir, main page]
Skip to main content

Advertisement

Springer Nature Link
Log in

Arterial calcification in diabetes

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Diabetes is associated with an increased prevalence of atherosclerotic vascular disease and cardiovascular mortality. In diabetic patients, medial calcification appears to be a strong independent predictor of cardiovascular mortality; it occurs particularly in those with neuropathy. Recent evidence suggests that medial calcification in diabetes is an active, cellmediated process, similar to that observed in patients with end-stage renal disease (ESRD), in which vascular smooth muscle cells (VSMCs) express a number of bone matrix proteins that act to either facilitate or regulate the calcification process. Several bone-associated proteins (eg, osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen, osteocalcin) have been demonstrated in histologic sections of vessels obtained from patients with diabetes or ESRD. In in vitro experiments, high glucose induced cell proliferation and expression of osteopontin in cultured VSMCs. Hypoxia had additive effects of hyperglycemia on VSMCs. In addition, uremic serum upregulates osteoblast transcription factor Cbfa1 and osteopontin expression in cultured VSMCs. The pathogenesis of vascular calcification in diabetes is not completely understood, although high glucose and other potential factors may play an important role by transforming VSMCs into osteoblast-like cells. Further understanding of the mechanism by which diabetes induces this complication is needed to design effective therapeutic strategies to intervene with this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. American Diabetes Association: 2000 Vital Statistics. http:// www.diabetes.org.

  2. McGuire DK, Granger CB: Diabetes and ischemic heart disease. Am Heart J 1999, 138:S366-S375.

    Article  PubMed  CAS  Google Scholar 

  3. United States Renal Data System 1999 Annual Report. Bethesda, MD: National Institute of Diabetes, Digestive and Kidney Diseases; 1999:34.

  4. McGuire DK: Influence of proteinuria on long-term outcome among patients with diabetes: the evidence continues to accumulate [editorial]. Am Heart J 2000, 139:934–935.

    Article  PubMed  CAS  Google Scholar 

  5. Berliner JA, Navab M, Fogelman AM, et al.: Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995, 91:2488–2496.

    PubMed  CAS  Google Scholar 

  6. Wexler L, Brundage B, Crouse J, et al.: Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association Writing Group. Circulation 1996, 94:1175–1192.

    PubMed  CAS  Google Scholar 

  7. Campbell GR, Campbell JH: Vascular smooth muscle and arterial calcification. Z Kardiol 2000, 89(suppl 2):54–62.

    Article  PubMed  Google Scholar 

  8. Virchow R: Sclerosis and ossification of arteries. In Cellular Pathology: As Bases Upon Physiological and Pathological Histology. New York: Dorer; 1971:404–408.

    Google Scholar 

  9. Bostrom K, Watson KE, Horn S, et al.: Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 1993, 91:1800–1809.

    PubMed  CAS  Google Scholar 

  10. Fitzpatrick LA, Severson A, Edwards WD, Ingram RT: Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis. J Clin Invest 1994, 94:1597–1604.

    PubMed  CAS  Google Scholar 

  11. Mori K, Shioi A, Jono S, et al.: Dexamethasone enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999, 19:2112–2118.

    PubMed  CAS  Google Scholar 

  12. Shanahan CM, Cary NR, Salisbury JR, et al.: Medial localization of mineralization-regulating proteins in association with Monckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 1999, 100:2168–2176.

    PubMed  CAS  Google Scholar 

  13. Shanahan CM, Proudfoot D, Tyson KL, et al.: Expression of mineralization-regulating proteins in association with human vascular calcification. Z Kardiol 2000, 89(suppl 2):63–68.

    Article  PubMed  CAS  Google Scholar 

  14. Guerin AP, London GM, Marchais SJ, Metivier F: Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000, 15:1014–1021.

    Article  PubMed  CAS  Google Scholar 

  15. Kiel DP, Hannan MT, Cupple LA, et al.: Low bone mineral density (BMD) is associated with coronary artery calcification. J Bone Miner Res 2000, 15 (suppl):S160.

    Google Scholar 

  16. Hak AE, Pols HA, van Hemert AM, et al.: Progression of aortic calcification is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 2000, 20:1926–1931.

    PubMed  CAS  Google Scholar 

  17. Stary HC: Natural history of calcium deposits in atherosclerosis progression and regression. Z Kardiol 2000, 89(suppl 2):28–35.

    Article  PubMed  Google Scholar 

  18. Lachman AS, Spray TL, Kerwin DM, et al.: A review of the problem and a description of a patient with involvement of peripheral, visceral and coronary arteries. Am J Med 1977, 63:615–622.

    Article  PubMed  CAS  Google Scholar 

  19. Edmonds ME: Medial arterial calcification and diabetes mellitus. Z Kardiol 2000, 89(suppl 2):101–104. Review article that summarized epidemiologic studies in which medial calcification is recognized as a strong predictor of cardiovascular morbidity and mortality in diabetic patients.

    Article  PubMed  Google Scholar 

  20. Hafner J, Keusch G, Wahl C, et al.: Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy. J Am Acad Dermatol 1995, 33:954–962.

    Article  PubMed  CAS  Google Scholar 

  21. Edwards RB, Jaffe W, Arrowsmith J, Henderson HP: Calciphylaxis: a rare limb and life threatening cause of ischaemic skin necrosis and ulceration. Br J Plast Surg 2000, 53:253–255.

    Article  PubMed  CAS  Google Scholar 

  22. Ahmed S, O’Neill KD, Hood AF, et al.: Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells. Am J Kidney Dis 2001, 37:1267–1276.

    PubMed  CAS  Google Scholar 

  23. Moe SM, O’Neill KD, Duan D, et al.: Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 2002, 61:638–647. This study demonstrated that expression of bone matrix proteins in arteries from uremic patients is correlated with the degree of vascular calcification and diabetes, indicating that the pathogenesis of vascular calcification in diabetes may be similar to that observed in patients with ESRD.

    Article  PubMed  Google Scholar 

  24. Lehto S, Niskanen L, Suhonen M, et al.: Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1996, 16:978–983.

    PubMed  CAS  Google Scholar 

  25. Kemmeren JM, Beijerinck D, van Noord PA, et al.: Breast arterial calcifications: association with diabetes mellitus and cardiovascular mortality. Work in progress. Radiology 1996, 201:75–78.

    PubMed  CAS  Google Scholar 

  26. Edmonds ME, Morrison N, Laws JW, Watkins PJ: Medial arterial calcification and diabetic neuropathy. BMJ 1982, 284:928–930.

    Article  PubMed  CAS  Google Scholar 

  27. Everhart JE, Pettitt DJ, Knowler WC, et al.: Medial arterial calcification and its association with mortality and complications of diabetes. Diabetologia 1988, 31:16–23.

    PubMed  CAS  Google Scholar 

  28. Detrano RC, Wong ND, French WJ, et al.: Prevalence of fluoroscopic coronary calcific deposits in high-risk asymptomatic persons. Am Heart J 1994, 127:1526–1532.

    Article  PubMed  CAS  Google Scholar 

  29. Shanahan CM, Cary NR, Metcalfe JC, Weissberg PL: High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest 1994, 93:2393–2402.

    PubMed  CAS  Google Scholar 

  30. Luo G, Ducy P, McKee MD, et al.: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997, 386:78–81.

    Article  PubMed  CAS  Google Scholar 

  31. Bucay N, Sarosi I, Dunstan CR, et al.: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998, 12:1260–1268.

    PubMed  CAS  Google Scholar 

  32. Aubin JE: Advances in the osteoblast lineage. Biochem Cell Biol 1998, 76:899–910.

    Article  PubMed  CAS  Google Scholar 

  33. Kockx MM, Muhring J, Bortier H, et al.: Biotin-or digoxigenin-conjugated nucleotides bind to matrix vesicles in atherosclerotic plaques. Am J Pathol 1996, 148:1771–1777.

    PubMed  CAS  Google Scholar 

  34. Watson KE, Parhami F, Shin V, Demer LL: Fibronectin and collagen I matrixes promote calcification of vascular cells in vitro, whereas collagen IV matrix is inhibitory. Arterioscler Thromb Vasc Biol 1998, 18:1964–1971.

    PubMed  CAS  Google Scholar 

  35. Davies MR, Hruska KA: Pathophysiological mechanisms of vascular calcification in end-stage renal disease. Kidney Int 2001, 60:472–479. An excellent review that discusses the mechanisms and risk factors for vascular calcification in patients with ESRD.

    Article  PubMed  CAS  Google Scholar 

  36. Shioi A, Nishizawa Y, Jono S, et al.: Beta-glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1995, 15:2003–2009.

    PubMed  CAS  Google Scholar 

  37. Bellows CG, Aubin JE, Heersche JN: Initiation and progression of mineralization of bone nodules formed in vitro: the role of alkaline phosphatase and organic phosphate. Bone Miner 1991, 14:27–40.

    Article  PubMed  CAS  Google Scholar 

  38. Murer H, Forster I, Hilfiker H, et al.: Cellular/molecular control of renal Na/Pi-cotransport. Kidney Int Suppl 1998, 65:S2-S10.

    Article  PubMed  CAS  Google Scholar 

  39. Jono S, McKee MD, Murry CE, et al.: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000, 87:E10-E17.

    PubMed  CAS  Google Scholar 

  40. Ducy P, Zhang R, Geoffroy V, et al.: Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997, 89:747–754.

    Article  PubMed  CAS  Google Scholar 

  41. Komori T, Yagi H, Nomura S, et al.: Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997, 89:755–764.

    Article  PubMed  CAS  Google Scholar 

  42. Moe SM, O’Neill KD, Duan D, Chen NX: Uremia induces Cbfa1 expression in vivo and in vitro in vascular smooth muscle cells. Kidney Int 2002, in press.

  43. Chen NX, O’Neill KD, Duan D, Moe SM: Phosphorus and uremic serum upregulate osteopontin expression in vascular smooth muscle cells. Kidney Int 2002, 62:1724–1731.

    Article  PubMed  CAS  Google Scholar 

  44. Hunt JL, Fairman R, Mitchell ME, et al.: Bone formation in carotid plaques: a clinicopathological study. Stroke 2002, 33:1214–1219.

    Article  PubMed  Google Scholar 

  45. Alipui C, Ramos K, Tenner TE Jr: Alterations of rabbit aortic smooth muscle cell proliferation in diabetes mellitus. Cardiovasc Res 1993, 27:1229–1232.

    Article  PubMed  CAS  Google Scholar 

  46. Oikawa S, Hayasaka K, Hashizume E, et al.: Human arterial smooth muscle cell proliferation in diabetes. Diabetes 1996, 45(suppl 3):S114-S116.

    PubMed  CAS  Google Scholar 

  47. Takemoto M, Yokote K, Yamazaki M, et al.: Enhanced expression of osteopontin by high glucose. Involvement of osteopontin in diabetic macroangiopathy. Ann N Y Acad Sci 2000, 902:357–363.

    Article  PubMed  CAS  Google Scholar 

  48. Sodhi CP, Phadke SA, Batlle D, Sahai A: Hypoxia stimulates osteopontin expression and proliferation of cultured vascular smooth muscle cells: potentiation by high glucose. Diabetes 2001, 50:1482–1490. Demonstrated that high glucose induced cell proliferation and osteopontin expression in VSMCs, and hypoxia had an additive effect of hyperglycemia on VSMCs. This suggests the pathophysiology of diabetic vascular calcification is multifactorial.

    Article  PubMed  CAS  Google Scholar 

  49. Rasmussen LM, Heickendorff L: Quantification of fibronectin in extracts of human aortae by an ELISA. Scand J Clin Lab Invest 1989, 49:205–210.

    PubMed  CAS  Google Scholar 

  50. Takemoto M, Yokote K, Yamazaki M, et al.: Enhanced expression of osteopontin by high glucose in cultured rat aortic smooth muscle cells. Biochem Biophys Res Comm 1999, 258:722–726.

    Article  PubMed  CAS  Google Scholar 

  51. Santilli SM, Fiegel VD, Knighton DR: Alloxan diabetes alters the rabbit transarterial wall oxygen gradient. J Vasc Surg 1993, 18:227–233.

    Article  PubMed  CAS  Google Scholar 

  52. Parhami F, Morrow AD, Balucan JL: Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation A possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler Thromb Vasc Biol 1997, 17:680–687.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Indiana University School of Medicine, 1001 West 10th Street, OPW 526, 46202, Indianapolis, IN, USA

    Neal X. Chen PhD

Authors
  1. Neal X. Chen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon M. Moe MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, N.X., Moe, S.M. Arterial calcification in diabetes. Curr Diab Rep 3, 28–32 (2003). https://doi.org/10.1007/s11892-003-0049-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-003-0049-2

Keywords

Search

Navigation