Role of the vascular endothelial sodium channel activation in the genesis of pathologically increased cardiovascular stiffness.

摘要: Cardiovascular (CV) stiffening represents a complex series of events evolving from pathological changes in individual cells the vasculature and heart which leads to overt tissue fibrosis. While vascular occurs naturally with ageing it is accelerated states insulin (INS) resistance, such as obesity type 2 diabetes. CV clinically manifested increased arterial pulse wave velocity myocardial fibrosis-induced diastolic dysfunction. A key question that remains how are these mechanistically linked. In this regard, heightened activation mineralocorticoid receptors (MR) hyperinsulinaemia occur INS resistance states. Further, downstream mediator MR receptor activation, endothelial cell Na+ channel (EnNaC), has recently been identified molecular determinant dysfunction fibrosis stiffening. Increased activity EnNaC results number negative consequences including cortical actin cytoskeleton cells, impaired NO release, oxidative stress-meditated destruction, permeability, stimulation an inflammatory environment. Such alterations impact function through regulation tone remodelling case heart, associated coronary reductions bioavailable leading failure preserved systolic (HFpEF). After brief discussion on mechanisms stiffness per se, review then focuses recent findings regarding role aldosterone enhance obesity/INS Finally, we discuss artery-mediated may lead cardiac HFpEF, condition especially pronounced obese diabetic females.