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.

Sulodexide Slows Down the Senescence of Aortic Endothelial Cells Exposed to Serum from Patients with Peripheral Artery Diseases

“…Inflammation and oxidative stress are the main disorders which contribute to impaired function of the vascular endothelium [1]. Cellular senescence, which is a natural process, being parallel t body aging, also happens in the endothelial cells and accelerates the formation of atherosclerotic changes [2].…”

Intracranial Vertebrobasilar Calcification in Patients with Ischemic Stroke Is a Predictor of Recurrent Stroke, Vascular Disease, and Death: A Case-Control Study

“…Statins are routinely used in various stroke etiologies as secondary preventions due to its its lipid-lowering, vasculoprotective, and pleiotropic effects, which might be of benefit for patients with VBC [26]. Subclinical endothelial dysfunction is present in senescent population, a fact that we can indirectly confirm by finding VBC in significantly older patients [2].…”

“…Atherosclerosis is a potentially modifiable driver of overall morbidity and mortality [1]. Arterial calcification is an integral part in the process of atherosclerosis and can be detected in up to 90% of atherosclerotic plaques [2,3]. Radiological presence and extent of calcification is hence used as a noninvasive marker for the burden of atherosclerosis [4].…”

Osteopontin in Vascular Calcification: A Central Player or Accidental Witness?

“…Recent preclinical and clinical studies have shown that vascular calcification is inexorable pathological process leading to mechanical rigidity and stiffness of vascular wall, endothelial dysfunction, development and accelerating atherosclerosis even in the absence of established cardiovascular (CV) disease [1][2][3]. Ectopic calcification is represented by several mutually counteracting molecular mechanisms, i.e., oxidative stress, microvascular inflammation, immune cell-to-cell cooperation, accumulation of lipids and extracellular proteins, vascular reparative systems, and metabolic disorders [4][5][6].…”