Role of Endothelial Cells in Myocardial Ischemia-Reperfusion Injury

Abstract

Minimizing myocardial ischemia-reperfusion injury has broad clinical implications and is a critical mediator of cardiac surgical outcomes. “Ischemic injury” results from a restriction in blood supply leading to a mismatch between oxygen supply and demand of a sufficient intensity and/or duration that leads to cell necrosis, whereas ischemia-reperfusion injury occurs when blood supply is restored after a period of ischemia and is usually associated with apoptosis (i.e. programmed cell death). Compared to vascular endothelial cells, cardiac myocytes are more sensitive to ischemic injury and have received the most attention in preventing myocardial ischemia-reperfusion injury. Many comprehensive reviews exist on various aspects of myocardial ischemia-reperfusion injury. The purpose of this review is to examine the role of vascular endothelial cells in myocardial ischemia-reperfusion injury, and to stimulate further research in this exciting and clinically relevant area. Two specific areas that are addressed include: 1) data suggesting that coronary endothelial cells are critical mediators of myocardial dysfunction after ischemia-reperfusion injury; and 2) the involvement of the mitochondrial permeability transition pore in endothelial cell death as a result of an ischemia-reperfusion insult. Elucidating the cellular signaling pathway(s) that leads to endothelial cell injury and/or death in response to ischemia-reperfusion is a key component to developing clinically applicable strategies that might minimize myocardial ischemia-reperfusion injury.

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

“…These findings and ours taken together suggest that hyperinsulinemia, plays a key role in the paradoxical protective effect of obesity in ischemia/ reperfusion injury through modulation of the RISK signaling. Insulin resistance may cause endothelial dysfunction and, therefore, influence myocardial susceptibility to reperfusion injury [21]. However, our present data do not show changes in endothelial-dependent vascular relaxation in response to 6 months of HFD feeding and, a recent ex vivo study using a mice model with vascular insulin resistance and vascular dysfunction, showed that insulin can directly activate myocardial PI3K/ Akt and protect against reperfusion injury despite the absence of functional insulin receptors in the endothelium [43].…”

“…It is generally accepted that reduction of reperfusion injury is associated with the activation of the RISK pathway components [18], including Akt, which is also a key enzyme in the insulin signaling pathway [19]. However, obesity with insulin resistance is characterized by endothelial dysfunction [20], and may negatively influence myocardial susceptibility to reperfusion injury [21].…”

Induction of Autophagy by Tongxinluo Through the MEK/ERK Pathway Protects Human Cardiac Microvascular Endothelial Cells From Hypoxia/Reoxygenation Injury

“…Besides, a capillary is next to almost every CM, and the distance between these 2 types of cells are very short (approximately 1-2 mm). 3,6 CMECs not only constitute the most important part of the microcirculation by supplying nutrition and oxygen but also possess unique CM-protective functions through HIF-a/ eNOS activation and neuregulin secretion during myocardial reperfusion injury. 4,35 Our study focused on the preservation of CMECs, or microcirculation protection in vitro, rather than CM protection itself.…”

“…Studies have indicated that endothelial cells are more vulnerable to reperfusion injury but that CMs are more sensitive to ischemic injury. 6,7 However, the protection of endothelial cells against reperfusion injury has received much less attention than CMs or the myocardium, as indicated by PubMed searches ("myocardial" or "cardiomyocyte" and "reperfusion injury," 14,207 articles vs. "cardiac" and "endothelial" and "reperfusion injury," 759 articles).…”

Quantitative Proteomics Analysis of Ischemia/Reperfusion Injury-Modulated Proteins in Cardiac Microvascular Endothelial Cells and the Protective Role of Tongxinluo

“…As a basic component of the myocardial microcirculation, CMECs have a critical role in the protection of cardiomyocytes against MIRI [3]. Although CMECs are more sensitive to the reperfusion injury than cardiomyocytes [4], endothelial cells (ECs) have received considerably less attention in relation to reperfusion injury. To date, few studies have been published to clarify the proteins in CMECs in MIRI and to describe the functions and interactions of the altered proteins.…”