Chronic Inflammation and Endothelial Dysfunction in Vascular Aging
The age-related decline and dysfunction of the vasculature kills a sizable fraction of humanity, directly through stroke and heart attack, and more indirectly through a number of other mechanisms. The rise of chronic inflammation with age can be blamed for much of this. Unresolved inflammatory signaling is highly disruptive to tissue function throughout the body. In the vasculature, it accelerates the altered macrophage behavior that lies at the root of atherosclerosis. It provokes some of the altered smooth muscle behavior that leads to hypertension as contraction and dilation of blood vessels become poorly controlled. It changes the behavior of cells in ways that lead to calcification of blood vessel walls.
The inner endothelium of blood vessels undergoes a range of detrimental functional changes with aging, and again many of these are driven at least in part by chronic inflammation. Disruption of this layer of the blood vessel wall appears to accelerate atherosclerosis, contribute to issues with the regulation of dilation and contraction, and produce leakage of the blood-brain barrier where blood vessels pass through the brain.
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 detrimental 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.
The prominence of inflammatory mediators, and the centrality of the inflammasome, have led scholars to set up studies to evaluate the possibility of inhibiting certain checkpoints from fighting the diseases of aging, so much so that there are ongoing trials to evaluate the efficacy of molecules that can inhibit the inflammasome from reducing cardiovascular risk. Blocking the inflammasome and reducing the blood concentrations of its products, first and foremost IL-1 beta and IL-18, could be an exciting target of future therapies, perhaps using monoclonal antibodies to tailor actions to specific targets. Compared with the past, today there are suggestive and fascinating pathways that hint at the possibility of counteracting the passage of time and the onset of age-related diseases. More pragmatically, the development of drugs of this type may enable successful aging.