The role of paracrine crosstalk between myeloid and endothelial cells in myocardial angiogenesis and infarcted heart repair.

Abstract

Ischemic heart disease is one of the leading causes of morbidity and mortality in the USA. It is mainly caused by the narrowing or occlusion of coronary arteries by plaque buildup, leading to a limited supply of oxygen and nutrients to the cardiac muscle. This results in necrotic death of cardiomyocytes (CMs). CM necrosis leads to the production of cytokines, chemokines, and damage-associated molecular patterns (DAMPs), which recruit immune cells from the bone marrow (BM) [1] . Infiltrated immune cells secrete proteases and cytokines that mediate inflammatory responses and fibroblast activation [1] . Subsequently, the damaged cardiac muscle is replaced with extracellular matrix produced by activated fibroblasts, leading to myocardial remodeling and dysfunction. Attempts to restore blood vessels (a.k.a. therapeutic angiogenesis) reduced fibrosis and improved the performance of the infarcted heart [2] . A possible underlying mechanism is that the supply of oxygen and nutrients via new blood vessels would preserve CM survival and support the health and function of remaining cardiovascular cells, thereby preventing adverse cardiac remodeling. Thus, therapeutic angiogenesis has been considered one of the important therapeutic approaches for ischemic heart diseases. Investigations