High-density lipoprotein (HDL) comprises a heterogeneous group of particles differing in size, density, and composition. HDL cholesterol (HDL-C) levels have long been suggested to indicate cardiovascular risk, inferred from multiple epidemiological studies. The failure of HDL-C targeted interventions and genetic studies has raised doubts on the atheroprotective role of HDL-C. The current consensus is that HDL-C is neither a biomarker nor a causative agent of cardiovascular disorders. With better understanding of the complex nature of HDL which comprises a large number of proteins and lipids with unique functions, recent focus has shifted from HDL quantity to HDL quality in terms of atheroprotective functions. The current research is focused on developing laboratory assays to assess HDL functions for cardiovascular risk prediction. Also, HDL mimetics designed based on the key determinants of HDL functions are being investigated to modify cardiovascular risk. Improving HDL functions by altering its composition is the key area of future research in HDL biology to reduce cardiovascular risk.

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.

Cardiovascular diseases (CVDs) are the leading cause of death in the world. Endothelial progenitor cells (EPCs) are currently being explored in the context of CVD risk. EPCs are bone marrow derived progenitor cells involved in postnatal endothelial repair and neovascularization. A large body of evidence from clinical, animal, and in vitro studies have shown that EPC numbers in circulation and their functionality reflect endogenous vascular regenerative capacity. Traditionally vitamin D is known to be beneficial for bone health and calcium metabolism and in the last two decades, its role in influencing CVD and cancer risk has generated significant interest. Observational studies have shown that low vitamin D levels are associated with an adverse cardiovascular risk profile. Still, Mendelian randomization studies and randomized control trials (RCTs) have not shown significant effects of vitamin D on cardiovascular events. The criticism regarding the RCTs on vitamin D and CVD is that they were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals. Overall, the association between vitamin D and CVD remains inconclusive. Recent clinical and experimental studies have demonstrated the beneficial role of vitamin D in increasing the circulatory level of EPC as well as their functionality. In this review we present evidence supporting the beneficial role of vitamin D in CVD through its modulation of EPC homeostasis.