Central role of eNOS in the maintenance of endothelial homeostasis

TY - JOUR

T1 - Central role of eNOS in the maintenance of endothelial homeostasis

AU - Heiss, Christian

AU - Rodriguez-Mateos, Ana

AU - Kelm, Malte

PY - 2015/5/10

Y1 - 2015/5/10

N2 - SIGNIFICANCE: Disruption of endothelial function is considered a key event in the development and progression of atherosclerosis. Endothelial nitric oxide synthase (eNOS) is a central regulator of cellular function that is important to maintain endothelial homeostasis.RECENT ADVANCES: Endothelial homeostasis encompasses acute responses such as adaption of flow to tissue's demand and more sustained responses to injury such as re-endothelialization and sprouting of endothelial cells (ECs) and attraction of circulating angiogenic cells (CAC), both of which support repair of damaged endothelium. The balance and the intensity of endothelial damage and repair might be reflected by changes in circulating endothelial microparticles (EMP) and CAC. Flow-mediated vasodilation (FMD) is a generally accepted clinical read-out of NO-dependent vasodilation, whereas EMP are upcoming prognostically validated markers of endothelial injury and CAC are reflective of the regenerative capacity with both expressing a functional eNOS. These markers can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity with NO representing a central signaling molecule.CRITICAL ISSUES: Improvements of reproducibility and observer independence of FMD measurements and definitions of relevant EMP and CAC subpopulations warrant further research.FUTURE DIRECTIONS: Endothelial homeostasis may be a clinical therapeutic target for cardiovascular health maintenance.

AB - SIGNIFICANCE: Disruption of endothelial function is considered a key event in the development and progression of atherosclerosis. Endothelial nitric oxide synthase (eNOS) is a central regulator of cellular function that is important to maintain endothelial homeostasis.RECENT ADVANCES: Endothelial homeostasis encompasses acute responses such as adaption of flow to tissue's demand and more sustained responses to injury such as re-endothelialization and sprouting of endothelial cells (ECs) and attraction of circulating angiogenic cells (CAC), both of which support repair of damaged endothelium. The balance and the intensity of endothelial damage and repair might be reflected by changes in circulating endothelial microparticles (EMP) and CAC. Flow-mediated vasodilation (FMD) is a generally accepted clinical read-out of NO-dependent vasodilation, whereas EMP are upcoming prognostically validated markers of endothelial injury and CAC are reflective of the regenerative capacity with both expressing a functional eNOS. These markers can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity with NO representing a central signaling molecule.CRITICAL ISSUES: Improvements of reproducibility and observer independence of FMD measurements and definitions of relevant EMP and CAC subpopulations warrant further research.FUTURE DIRECTIONS: Endothelial homeostasis may be a clinical therapeutic target for cardiovascular health maintenance.

KW - Endothelial Cells

KW - Homeostasis

KW - Humans

KW - Nitric Oxide Synthase Type III

U2 - 10.1089/ars.2014.6158

DO - 10.1089/ars.2014.6158

M3 - Article

C2 - 25330054

SN - 1523-0864

VL - 22

SP - 1230

EP - 1242

JO - Antioxidants & redox signaling

JF - Antioxidants & redox signaling

IS - 14

ER -