Recent developments in vascular biology.

Abstract

The field of vascular biology has transformed dramatically in recent years as new research has elucidated complex roles of novel proteins, stem/progenitor/hematopoietic cells, and miRNAs as well as redox signaling in vascular development, vascular tone regulation and disease in preclinical models and clinical settings. Review of this body of work highlights seminal findings and new developments that emphasize and illuminate underlying principles and historical connections. In the 1980s, there was the frenzied search for the identity of the Endothelium-Derived Relaxing Factor (EDRF; ie, NO).1,2 In the 1990s, the elucidation of myriad EDHFs (hyperpolarizing factors, eg, H2O2, K+, arachidonic acid metabolites) expanded endothelial cell complexity beyond NO.3–5 In the 2000s, the endothelial cell generation and overall cardiovascular effects of H2S were hotly pursued.6,7 In the 2010s, the role of the perivascular adipose tissue (PVAT) derived relaxing and contractile factors in vascular regulation under physiological and disease promoting conditions (eg, diet-induced obesity, metabolic syndrome) has emerged as a new integrative vascular issue of import because of the obesity epidemic.8 Critically important mechanisms continue to be sources of interest and renewed research. Indeed, the panoply of endothelium-derived factors that regulate vascular tone continues to grow, and identifying new ones will only enhance our understanding of the diverse factors that regulate vascular tone and blood flow in context-dependent ways. As elucidated in the article by Zhang et al, entitled “H2O2-induced dilation in human coronary arterioles: role of protein kinase G dimerization and large-conductance Ca2+-activated K+ channel activation,” redox-mediated VSMC K+-channel opening ultimately leads to relaxation and dilation in coronary blood vessels.9 Similarly, PPAR-γ stimulated Regulatory G-protein S 5 (RGS5)-control of Protein Kinase C-mediated opening of calcium-activated …