Role of endothelial colony forming cells (ECFCs) Tetrahydrobiopterin (BH4) in determining ECFCs functionality in coronary artery disease (CAD) patients

Abstract

Nitric oxide (NO.) is critical for functionality of endothelial colony forming cells (ECFCs). Dimerization of endothelial nitric oxide synthase (eNOS) is must to produce NO. and tetrahydrobiopterin (BH4) plays a crucial role in stabilizing this state. We investigated BH4 level in ECFCs and its effect on ECFCs functionality in CAD patients. Intracellular biopterin levels and ECFCs functionality in terms of cell viability, adhesion, proliferation, in vitro wound healing and angiogenesis were assessed. Guanosine Triphosphate Cyclohydrolase-1 (GTPCH-1) expression was studied in ECFCs. Serum total reactive oxygen/nitrogen species was measured and effect of nitrosative stress on ECFC’s biopterins level and functionality were evaluated by treating with 3-morpholino sydnonimine (SIN-1). BH4 level was significantly lower in ECFCs from CAD patients. Cell proliferation, wound closure reflecting cellular migration as well as in vitro angiogenesis were impaired in ECFCs from CAD patients. Wound healing capacity and angiogenesis were positively correlated with ECFC’s BH4. A negative effect of nitrosative stress on biopterins level and cell functionality was observed in SIN-1 treated ECFCs. ECFCs from CAD exhibited impaired functionality and lower BH4 level. Association of BH4 with wound healing capacity and angiogenesis suggest its role in maintaining ECFC’s functionality. Oxidative stress may be a determinant of intracellular biopterin levels.

Recent advances in endothelial colony-forming cells: from the transcriptomic perspective

“…ECFC dysfunction is correlated with the onset of cardiovascular disorders, especially CAD [ 79 – 81 ]. The miRNA sequencing analysis showed a significant upregulation of miR-410-3p, miR-497-5p, and miR-2355-5p in CAD-ECFCs.…”

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease

“…CAD is caused by excessive lipid accumulation in the vessel wall because of long-term exposure to lifestyle risk factors such as high sugar and fat. This accumulation results in reduced endothelial function, which in turn leads to stenosis and blockage [5]. A study has shown that vascular regeneration in the infarcted areas of the heart and the construction of new vascular transport channels at the onset of CAD are essential for alleviating CAD symptoms [6].…”