Vascular calcium signalling and ageing

Abstract

Changes in cellular Ca²⁺ levels have major influences on vascular function and blood pressure regulation. Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) orchestrate vascular activity in distinct ways, often involving highly specific fluctuations in Ca²⁺ signalling. Ageing is a major risk factor for cardiovascular diseases, but the impact of ageing per se on vascular Ca²⁺ signalling has received insufficient attention. We reviewed the literature for age-related changes in Ca²⁺ signalling in relation to vascular structure and function. Vascular tone dysregulation in several vascular beds has been linked to abnormal expression or activity of SMC voltage-gated Ca²⁺ channels, Ca²⁺ -activated K⁺ channels or TRPC6 channels. Some of these effects were linked to altered caveolae density, microRNA expression or 20-HETE abundance. Intracellular store Ca²⁺ handling was suppressed in ageing mainly via reduced expression of intracellular Ca²⁺ release channels, and Ca²⁺ reuptake or efflux pumps. An increase in mitochondrial Ca²⁺ uptake, leading to oxidative stress, could also play a role in SMC hypercontractility and structural remodelling in ageing. In ECs, ageing entailed diverse effects on spontaneous and evoked Ca²⁺ transients, as well as structural changes at the EC-SMC interface. The concerted effects of altered Ca²⁺ signalling on myogenic tone, endothelium-dependent vasodilatation, and vascular structure are likely to contribute to blood pressure dysregulation and blood flow distribution deficits in critical organs. With the increase in the world's ageing population, future studies should be directed at solving specific ageing-induced Ca²⁺ signalling deficits to combat the imminent accelerated vascular ageing and increased risk of cardiovascular diseases.

Keywords: ageing; blood flow dysregulation; calcium signalling; endothelium; hypertension; vascular dysfunction; vascular smooth muscle.