VSMC phenotype regression induced by hypoxia is the key to unlocking VSMC solid cell cord

Abstract

Abstract Coronary heart disease is the world's leading cause of death. Vasculogenesis, sprouting angiogenesis, intussusceptive angiogenesis, coalescent angiogenesis, vessel co-option, vasculogenic mimicry and arteriogenesis are the seven main ways of collateral vessel development. However, none of the seven methods of collateral vessel development is sufficient to timely rescue a large number of dying myocardial cells in the myocardial infarction area. In this study, we first proposed the hypothesis that vascular smooth muscle cell (VSMC) solid cell cords are precursors of collateral vessels and confirmed the existence of VSMC solid cell cords in the heart. In addition, we further confirmed that intracellular acidification induced by hypoxia can promote VSMC phenotype regression (transformation from synthetic phenotype to contractile phenotype) by downregulating AMP activated protein kinase (AMPK) phosphorylation level, which prepares for the rapid opening of VSMC solid cell cords to timely rescue dying myocardial cells. We hope that this innovative and challenging hypothesis can provide some inspiration to cardiovascular researchers and contribute to the cause of human health.