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Pathogenesis of the Plaque Vulnerability in Diabetes Mellitus

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Mechanisms of Vascular Defects in Diabetes Mellitus

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 17))

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Abstract

Atherosclerosis leads to narrowing of vessels and acute coronary syndrome resulting in ischemic events due to either vasospasm or decreased blood flow. Atherosclerosis and acute coronary syndrome are more common in diabetes mellitus. Hyperglycemia and hypercholesterolemia in diabetes predispose the arteries to plaque development. Smoking, hypertension, male sex, and family history or genetic susceptibility are other predisposing factors for plaque development. Depending on the size, morphology, and symptoms of the patients, plaques can be classified as stable and unstable plaques. Unstable plaques are characterized by the presence of thin fibrous cap, necrotic core, and proliferation of vascular smooth muscle cells, angiogenesis and calcification. Plaque formation initiates with fatty streak and progresses through atheroma, atheromatous plaque to fibroatheromatous plaque. Fibroatheromatous plaques with thick fibrous cap are stable plaques. Thinning of the fibrous cap makes a plaque unstable, prone to rupture and thrombus formation. Mechanisms such as increased inflammation, foam cell deposition, impaired repair mechanism, endothelial cell dysfunction, vascular smooth muscle cell proliferation, angiogenesis, intra-plaque hemorrhage, and calcification which facilitate the plaque rupture are increased in diabetes mellitus. Thus, diabetes mellitus increases the prevalence of plaque formation and rupture. Diabetes mellitus affects various cellular and molecular effectors involved in plaque development and rupture. Understanding these cellular and molecular effectors and involved mechanisms in association with diabetes mellitus is essential for the development of potential therapeutic strategies. This review is a critical overview on the effect of hyperglycemia in diabetes mellitus on the pathogenesis of plaque formation and rupture.

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Acknowledgement

This work was supported by research grants R01 HL112597, R01 HL116042, and R01 HL120659 to DK Agrawal from the National Heart, Lung and Blood Institute, National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Clinical & Translational Science, Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE, 68178, USA

    Vikrant Rai & Devendra K. Agrawal Ph.D., M.B.A., M.S., F.A.H.A.

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  1. Vikrant Rai
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  2. Devendra K. Agrawal Ph.D., M.B.A., M.S., F.A.H.A.
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Corresponding author

Correspondence to Devendra K. Agrawal Ph.D., M.B.A., M.S., F.A.H.A. .

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Editors and Affiliations

  1. Division of Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

    C.C. Kartha

  2. Division of Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

    Surya Ramachandran

  3. Translational Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India

    Radhakrishna M. Pillai

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Rai, V., Agrawal, D.K. (2017). Pathogenesis of the Plaque Vulnerability in Diabetes Mellitus. In: Kartha, C., Ramachandran, S., Pillai, R. (eds) Mechanisms of Vascular Defects in Diabetes Mellitus. Advances in Biochemistry in Health and Disease, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-60324-7_4

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