Vascular biology of ageing—Implications in hypertension

Abstract

Ageing is associated with functional, structural and mechanical changes in arteries that closely resemble the vascular alterations in hypertension. Characteristic features of large and small arteries that occur with ageing and during the development of hypertension include endothelial dysfunction, vascular remodelling, inflammation, calcification and increased stiffness. Arterial changes in young hypertensive patients mimic those in old normotensive individuals. Hypertension accelerates and augments age-related vascular remodelling and dysfunction, and ageing may impact on the severity of vascular damage in hypertension, indicating close interactions between biological ageing and blood pressure elevation. Molecular and cellular mechanisms underlying vascular alterations in ageing and hypertension are common and include aberrant signal transduction, oxidative stress and activation of pro-inflammatory and pro-fibrotic transcription factors. Strategies to suppress age-associated vascular changes could ameliorate vascular damage associated with hypertension. An overview on the vascular biology of ageing and hypertension is presented and novel molecular mechanisms contributing to these processes are discussed. The complex interaction between biological ageing and blood pressure elevation on the vasculature is highlighted. This article is part of a Special Issue entitled: CV Ageing.

The anti‐ageing hormone klotho induces Nrf2‐mediated antioxidant defences in human aortic smooth muscle cells

“…Activation of RAS and down‐regulation of Nrf2 signalling and antioxidant gene expression are associated with the development of age‐related vascular diseases 24. In this study, we provide the first evidence that the soluble form of the anti‐ageing protein, klotho, activates Nrf2 in HASMC, resulting in an enhanced expression of the antioxidant enzymes HO‐1 and Prx‐1 which are regulated by ARE in their promoter regions.…”

Drug Treatment of Hypertension: Focus on Vascular Health

“…The vascular endothelium is a monolayer of cells that forms the lining of all blood vessels and plays an essential role in vascular function through the synthesis and release of biologically active substances that act in an autocrine or paracrine fashion to influence vascular tone and function 4,6 . Examples include NO, prostacyclin (PGI 2 ) and endothelium derived hyperpolarising factor (EDHF) 4 .…”

“…Vasodilator responses are mainly related to NO production, which is released by healthy and intact endothelium via eNOS 1,6 . Reduced NO bioavailability is a key characteristic of endothelial dysfunction, and results in part from increased ROS generation which inhibits eNOS activity 6 .…”

“…Hypertension-associated cardiovascular complications are prevented or ameliorated by antihypertensive drugs through blood pressure lowering and through direct effects on target 6 dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Signalling through these pathways contribute to extra-cellular matrix remodelling and result in further vascular fibrosis 2 .…”

“…Healthy endothelium has a vasodilator, anti-inflammatory and anti-thrombotic phenotype, whilst endothelial dysfunction is characterised by an endothelium that is pro-inflammatory, pro-thrombotic with impaired vasodilator responses 6 . Endothelial dysfunction is a central component of the phenotypical changes that occur in the development of hypertension and is associated with increased atherosclerosis and cardiovascular risk 1 .…”