title: Arterial ageing: from endothelial dysfunction to vascular calcification.
abstract: Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed.
authors.affiliation: Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Tesauro
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mauriello
authors.affiliation: Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Rovella
authors.affiliation: Biochemistry Laboratory, Istituto Dermopatico Immacolata IDI-IRCCS, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Annicchiarico-Petruzzelli
authors.affiliation: Department of Internal Medicine, Catholic University, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cardillo
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.|Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK.
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.affiliation: Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: N
authors.identifier: http://orcid.org/0000-0001-7671-0015
authors.initials: N
authors.lastname: Di Daniele
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000503:physiopathology; D013312:Stress, Physiological / Q000502:physiology; D061205:Vascular Calcification / Q000503:physiopathology*
keywords: ageing; atherosclerosis; cell death; endothelial plaques; nitric oxide; vascular calcification