Dear Colleagues,

Endothelial cells (ECs) form the inner lining of blood vessels and play a major role in maintaing blood vessel integrity, also by actively participating in the transduction of signals between the bloodstream and surrounding tissues. In physiological conditions, ECs regulate vascular tone through the release of the gaseous mediator nitric oxide and prevent uncontrolled platelet aggregation and activation of the coagulation cascade.

Endothelial dysfunction, which represents the first step of vascular alterations, results from the reduced EC ability to release vasodilatory mediators and the acquisition of a prothrombotic and proinflammatory phenotype. The dysfunctional endothelial phenotype is recapitulated in senescent ECs, which accumulate in the vasculature during aging and in the presence of inflammatory stimuli and cardiovascular risk factors. Despite their growth arrest, senescent ECs display a high metabolic rate, which is required to sustain the mainteinance of their senescence-associated proinflammatory phenotype (SASP). In this framework, increased oxidative stress represents a major mechanism contributing to the onset of premature EC senescence and dysfunction induced by most cardiovascular risk factors and systemic metabolic derangements. Also, senescent ECs participate in the maintenance of a pro-oxidant microenvironment that contributes to the spreading of senescence to neighbouring vascular cells.

Endothelial dysfunction significantly contributes to the onset of a number of age-related diseases, including cardiovascular diseases, type 2 diabetes, neurodegenerative disorders, and age-related macular degeneration. Several approaches can be used to evaluate endothelial dysfunction, including functional tests, imaging studies, as well as the assessment of circulating biomarkers related to the the proinflammatory and procoagulant EC phenotype.

Identifying endothelial dysfunction at its earliest stages would be of uttermost importance to define interventional strategies aimed at preventing or postponing the detrimental outcomes associated with increasing cardiovascular morbidity. To this regard, pharmacological and dietary interventions targeting senescent ECs or aimed at reshaping EC metabolism and interaction with other vascular and immune cells are showing promising results in micro- and macrovascular diseases. Notably, antioxidant compounds have been extensively invoked to ameliorate EC senescence, that invariably precedes age-related vascular degeneration.

This Special Issue aims to collect papers – either original manuscripts or reviews – focused on the role of EC dysfunction in the context of human ageing and age-related diseases. Observational, mechanistic, and interventional in vitro or in vivo studies exploring the impact of oxidative stress on EC senescence and dysfunction and the effects of antioxidant compunds on the age-related vascular dysfunction are welcomed.

Dr. Jacopo Sabbatinelli
Dr. Angelica Giuliani
Guest Editors

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• Endothelial dysfunction
• aging
• age-related diseases
• inflammaging
• endothelial cells
• cardiovascular disease
• frailty