Endothelial Progenitor Cells in Heart Failure: an Authentic Expectation for Potential Future Use and a Lack of Universal Definition

Abstract

Congestive heart failure (CHF) is a prevalent disease (especially among the elderly) with high mortality and morbidity rates. The pathological hallmark of CHF is a loss of cardiomyocytes leading to cardiac fibrosis and dysfunctional cardiac remodeling, which culminates in organ failure. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to maintenance of the integrity of endothelial wall and protect ischemic myocardium through forming new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Despite its potential, little is known about EPCs and their function in CHF. Here, we define EPC and its role in health and CHF, highlighting their contributions as a cornerstone in the maintenance of a healthy endothelium. Thereafter, we explore the behavior and relevance of EPCs in the pathophysiology of CHF, their prognostic importance, and possible utilization of EPCs as therapy for CHF. Lastly, the restrictions surrounding the use of EPCs in clinical practice will be discussed.

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4

“…Our study further demonstrated that Tβ4 also enhanced diabetic EPC migration and tubule formation capability by 50% and 25%, respectively, compared with non-Tβ4 treated EPCs, which is shown to be mediated by PI3K/Akt/ endothelial nitric oxide synthase (eNOS) signal pathway [31]. It is known that EPCs-mediated endothelial cell repair is impaired in coronary heart disease [17]. Thus, Tβ4 can be potentially be used to enhance migration of bone marrow derived EPCs to the ischemic myocardium to aid in endothelial cell repair.…”

“…Endothelial dysfunction plays a primary role in the development of vascular complications associated with diabetes and cardiovascular disease [3,17]. Furthermore, it was also reported that Tβ4 upregulation occurs following myocardial injuries such as MI, providing substrates for neovascularization and paracrine signals for endogenous stem cell recruitment to assist in wound repair [18].…”

TRP Channels in Angiogenesis and Other Endothelial Functions

“…The role of TRPC3 in angiogenesis has also been evaluated in EPCs (Dragoni et al, 2013). As stated above, EPCs are adult stem cells having the ability to differentiate into ECs, and thereby they promote postnatal vasculogenesis and endothelial repair after vascular intima injury (Djohan et al, 2018). Molecular and pharmacological inhibition of TRPC3, using siRNA and Pyr3 respectively, abrogated VEGF-induced Ca 2+ response and inhibited proliferation of EPCs (Dragoni et al, 2013).…”

SDF‐1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception

“…The discovery that mononuclear cells can home to sites of hypoxia and enhance neo‐angiogenesis has faced the possibility of using isolated hematopoietic stem cells or endothelial progenitor cells (EPC) for therapeutic vasculogenesis . However, infusion of EPC did not improve neovascularization suggesting that a not‐yet‐defined functional characteristic (eg, chemokine or integrin receptors mediating homing) is essential for EPC‐mediated vascular augmentation after ischaemia . During endothelial repair after vascular injury and during tumour angiogenesis, BMDC do not seem to be involved in re‐endothelialization, stressing their supportive role over trans‐differentiation .…”