From:  Endothelial dysfunction and vascular stiffness: molecular drivers of cardiovascular aging

 Key molecular mechanisms of endothelial dysfunction in aging.

MechanismMolecular featuresFunctional consequenceReferences
Reduced NO bioavailability↓ eNOS activity, ↑ ADMA, tetrahydrobiopterin deficiencyImpaired vasodilation, pro-thrombotic state[6, 1315]
Oxidative stress↑ NADPH oxidase, mitochondrial ROS, eNOS uncouplingNO degradation, peroxynitrite formation[1517, 3133]
InflammationNF-κB activation, ↑ IL-6, ↑ TNF-α, adhesion moleculesEndothelial activation, leukocyte adhesion[18, 33, 46]
Senescencep53/p21, p16/Rb, SASP secretionIrreversible growth arrest, pro-inflammatory milieu[17, 18, 29, 30, 40]

ADMA: asymmetric dimethylarginine; eNOS: endothelial nitric oxide synthase; IL-6: interleukin-6; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NO: nitric oxide; ROS: reactive oxygen species; SASP: senescence-associated secretory phenotype; TNF-α: tumor necrosis factor-alpha.