Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

Abstract

Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.

Keywords: cellular senescence; chronic inflammation; endothelial dysfunction; inflamm-ageing; vascular alterations.

Figure 1

Pathophysiological elements of vascular damage in T2D, with a focus on the dysregulation of the balance between factors regulating vasoconstriction and vasodilation. Endothelial nitric oxide synthase (eNOS), advanced glycation end products (AGEs), protein kinase C (PKC), nitric oxide (NO), and nuclear factor kappa B (NF-κB).

Figure 2

The evolution of vascular damage in relation to ever-increasing endothelial dysfunction as man ages, showing the pathogenetic factors that favor cellular damage.