NYMC Faculty Publications

Advances of Effects of Copper on Cardiovascular Health

First Page

213

Last Page

228

Document Type

Book Chapter

Publication Date

9-12-2017

Department

Biochemistry and Molecular Biology

Abstract

Coronary heart disease is a major cause of death in developed countries. The disease is primarily caused by severe atherosclerosis (AS). According to the ‘response to injury’ hypothesis, AS is initiated by series of inflammatory events and eventual damage to the endothelium. As a main regulator of hemodynamic homeostasis, the endothelium in the vasculature functions as a physical barrier, as well as an ‘endocrine depot’ for the synthesis of vasoactive agents that exert cardioprotective activities. The intrinsic ability to sense humoral and hemodynamic stimuli endows the endothelium with a broad range of bioactivities, including, the local modulation of vascular tone and structure, the control of proliferation and migration of vascular smooth muscle cells, and the dynamic regulation of the adhesion and extravasation of leukocytes. Accordingly, impairment of endothelial cell function and their enhanced permeability to atherogenic lipoproteins are major pathological events that initiate AS. Atherosclerotic lesions are characterized by chronic inflammation of the vessel wall initiated by leukocyte recruitment, adhesion, and enhanced retention of low-density lipoprotein (LDL) within activated endothelium. Migration and aggregation of LDL into the subendothelium coupled with subsequent lipid accumulation within macrophages support foam cell formation. Elucidating molecules and pathways essential for the preservation of vascular endothelial integrity and function will provide insights that could lead to discovery of efficient therapeutic targets for the treatment of atherosclerotic vascular disease. This chapter will explore the contributions of copper in controlling vascular endothelial cell activation and inflammation. Evidences on cardioprotection by copper and its association with cuproenzymes that control mitochondrial energy generation, collagen and elastin cross-linking, iron-transport, and degradation of superoxide will be summarized.

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