Endothelial Progenitor Cells Dysfunctions and Cardiometabolic Disorders: From Mechanisms to Therapeutic Approaches

Abstract

Metabolic syndrome (MetS) is a cluster of several disorders, such as hypertension, central obesity, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease. Despite health policies based on the promotion of physical exercise, the reduction of calorie intake and the consumption of healthy food, there is still a global rise in the incidence and prevalence of MetS in the world. This phenomenon can partly be explained by the fact that adverse events in the perinatal period can increase the susceptibility to develop cardiometabolic diseases in adulthood. Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing cardiovascular diseases (CVD) and metabolic disorders later in life. It has been shown that alterations in the structural and functional integrity of the endothelium can lead to the development of cardiometabolic diseases. The endothelial progenitor cells (EPCs) are circulating components of the endothelium playing a major role in vascular homeostasis. An association has been found between the maintenance of endothelial structure and function by EPCs and their ability to differentiate and repair damaged endothelial tissue. In this narrative review, we explore the alterations of EPCs observed in individuals with cardiometabolic disorders, describe some mechanisms related to such dysfunction and propose some therapeutical approaches to reverse the EPCs dysfunction.

Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction

“…In addition, we used immunofluorescence to measure CD34 expression, a marker of tube-forming capacity [45], a property related to ECFCs, and observed decreased CD34 expression in IUGR-ECFCs compared with CTRL-ECFCs. A negative correlation between circulating EPC numbers and multiple cardiovascular risks at adulthood has been observed in several human studies [46][47][48][49]. However, in individuals born with low birth weight, data are relatively scarce.…”

Regulation of Endothelial Progenitor Cell Functions in Ischemic Heart Disease: New Therapeutic Targets for Cardiac Remodeling and Repair

“…Human induced pluripotent stem cells can reproducibly form isolated homogeneous and stable populations with umbilical cord blood ECFC properties, which include high proliferative and no teratoma-forming potential ( 146 ). In addition, different degrees of tissue ischemia, hypoxia, inflammation, and oxidative stress in ischemic diseases cause EPCs to exhibit reduced proliferative capacity, dysfunction, and reduced angiogenic capacity, resulting in a low survival rate of transplanted cells in host tissues ( 147 ). EPCs and EPC-derived EXs can be used to correct disease-induced cellular dysfunction by enhancing in vivo functions through genetic modification and preconditioning.…”

Functions of the endothelium and its role in hematopoietic cell transplantation

“…Endothelial dysfunction is one of the earliest signs and an important event in the onset of the atherosclerotic process and insulin resistance [42,43]. The reduction in NO activity caused by 1) decreased eNOS expression, 2) insufficient substrate (L-arginine) or co-factors (tetrahydrobiopterin or BH4) for eNOS or the presence of antagonists, 3) impaired eNOS activation (due to increased caveolin), and 4) increased degradation rate of NO [41].…”