Endothelial progenitors in pulmonary hypertension: new pathophysiology and therapeutic implications: Fig. 1—

Abstract

Pulmonary hypertension is a progressive and disabling disease with as yet unclear pathogenesis, limited treatment options and poor prognosis. This is why the discovery of new pathogenic mechanisms and therapeutic strategies are needed. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in endothelial homeostasis, as well as physiological and pathological angiogenesis. Experimental and clinical studies have been conducted to understand the possible contribution of EPCs to the pathogenesis of pulmonary hypertension. Conflicting results have been obtained regarding the protective versus harmful effects of EPCs on the pulmonary vasculature. However, preliminary clinical trials using EPCbased therapies in patients with pulmonary hypertension show benefit of this approach, thus revealing EPCs as potential therapeutic targets.This review critically summarises the complex and conflicting data on EPCs and pulmonary hypertension, in both humans and animals, putting them into the context of lung (patho)physiology.The resulting scenario identifies EPCs as a novel and fascinating tool to study pathophysiology and therapy in the setting of pulmonary hypertension.

High proliferative potential endothelial colony-forming cells contribute to hypoxia-induced pulmonary artery vasa vasorum neovascularization

“…Given that ECFC may contribute to angiogenesis (8,9) and also exhibit a hierarchy of functional cell surface markers, we carried out immunofluorescence analysis on sections of the MPA to examine the expression of endothelial and progenitor markers such as CD31, CD34, and CD133 in the adventitial VV to characterize the nature of the cells in the normal (control) and expanding (hypoxic) VV. Increased VV density was demonstrated by the increased numbers CD31…”

“…The true identity of an EPC and the cell surface markers used to identify those cells remains controversial since EPC have been isolated from different sources and different species. Generally, cell surface antigens including CD34 and CD133 (8) have been used to identify endothelial progenitor phenotype, whereas CD31 and CD105 have been used to identify endothelial-specific phenotype (1). CD31 (PECAM-1) is known to be involved in endothelial cell proliferation, intercellular junction formation, and inflammatory cell trafficking through the endothelial monolayer (24,35,42).…”

“…Given that EPC have been implicated in the vascular remodeling process (8) and that ECFC possess increased proliferative capacity, we aimed to investigate the presence of a different hierarchy of proliferative cells in VVEC-Co and VVEC-Hx. An established method for ECFC isolation and identification is the single-cell clonogenic assay, where single EC would give rise to populations with different proliferative potential (21).…”

“…Recently, endothelial progenitor cells (EPC) have been implicated in the remodeling process in vascular physiological and pathological responses (7,8). However, since their discovery by Asahara et al in 1997 (2), there has been considerable controversy with regard to their origin, sources, and identities.…”

Circulating Endothelial Cell Quantification by Microfluidics Chip in Pulmonary Arterial Hypertension

“…First, endothelial progenitor cells (EPCs) are bone marrow derived and contribute to vascular repair. We, and others, have shown that EPCs (CD34 1 /KDR 1 /CD31 1 /CD45 2 ) are decreased in PAH (5,6). Second, circulating endothelial cells (CECs) have been discussed as potential biomarkers in PAH with or without congenital heart disease.…”