Endothelial Senescence and the Chronic Vascular Diseases: Challenges and Therapeutic Opportunities in Atherosclerosis

Abstract

Atherosclerosis is probably one of the paradigms of disease linked to aging. Underlying the physiopathology of atherosclerosis are cellular senescence, oxidative stress, and inflammation. These factors are increased in the elderly and from chronic disease patients. Elevated levels of oxidative stress affect cellular function and metabolism, inducing senescence. This senescence modifies the cell phenotype into a senescent secretory phenotype. This phenotype activates immune cells, leading to chronic systemic inflammation. Moreover, due to their secretory phenotype, senescence cells present an increased release of highlighted extracellular vesicles that will change nearby/neighborhood cells and paracrine signaling. For this reason, searching for specific senescent cell biomarkers and therapies against the development/killing of senescent cells has become relevant. Recently, senomorphic and senolityc drugs have become relevant in slowing down or eliminating senescence cells. However, even though they have shown promising results in experimental studies, their clinical use is still yet to be determined.

Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm

“…As previously described, critical lengths of telomeres lead to direct telomere DNA damage and impair cellular function and metabolism. This leads to senescence and changes the phenotype of the cell to a senescence secretory phenotype [ 40 ]. Therefore, our next interest was to determine whether the observed γH2AX-related senescent cells express SASP secretomes.…”

Retinal and Choroidal Thinning—A Predictor of Coronary Artery Occlusion?

“…Vascular endothelium damage is the sight of the initial atherosclerosis development [ 53 ]. Affected endothelium is unable to maintain vascular diameter, tone and blood flow (due to reduced nitric oxide and increased reactive oxygen species, as well as endothelin receptor-1) [ 54 ]. On the other hand, hyperlipidemia acts as one of the main risk factors of coronary heart disease.…”

Cellular Senescence and Ageing: Mechanisms and Interventions

“…Drugs with senomorphic properties have also been studied for their effectiveness into treating atherosclerosis. For example, drugs like rapamycin and ruxolitinib inhibit intracellular mediators, such as the kinase mTOR, that play a key role in SASP initiation ( Ramírez et al, 2022 ).…”