4.4 Article Proceedings Paper

Endothelium in Coronary Macrovascular and Microvascular Diseases

Journal

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 78, Issue -, Pages 19-29

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000001089

Keywords

coronary artery disease; coronary microvascular dysfunction; endothelial function; endothelium; nitric oxide; vasospastic angina

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan [16K19383, 17K15983]
  2. Grants-in-Aid for Scientific Research [16K19383, 17K15983] Funding Source: KAKEN

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This article summarizes the role of endothelial cells in regulating vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases, with a special emphasis on the mechanisms and clinical implications of coronary microvascular dysfunction (CMD).
The endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size-dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endotheliumindependent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.

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