Novel Contributors and Mechanisms of Cellular Senescence in Hypertension-Associated Premature Vascular Aging

Abstract

Hypertension has been described as a condition of premature vascular aging, relative to actual chronological age. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in hypertension. Nonetheless, the precise mechanisms that underlie the aged phenotype of arteries from hypertensive patients and animals remain elusive. Cellular senescence is an age-related physiologic process in which cells undergo irreversible growth arrest. Although controlled senescence negatively regulates cell proliferation and promotes tissue regeneration, uncontrolled senescence can contribute to disease pathogenesis by presenting the senescence-associated secretory phenotype, in which molecules such as proinflammatory cytokines, matrix metalloproteases, and reactive oxygen species are released into tissue microenvironments. This review will address and critically evaluate the current literature on the role of cellular senescence in hypertension, with particular emphasis on cells types that mediate and modulate vascular function and structure.

78 kDa Glucose-Regulated Protein Attenuates Protein Aggregation and Monocyte Adhesion Induced by Angiotensin II in Vascular Cells

“…Although the contribution of protein aggregates to aging-related CVDs including hypertension has not been thoroughly investigated, a reduction in the buffering capacity of the proteostasis network in the vasculature may increase the risk of aortic stiffness and hypertension [8,36]. Specifically, our data presented here support the concept that the induction of ER stress and subsequent UPR by AngII potentially play a causative role in immune cell infiltration in the vasculature [7,37]. In pulmonary artery smooth muscle cells, endothelin-1 has been shown to stimulate inflammatory responses, including THP-1 adhesion via ER stress and UPR signaling [38].…”

Immunosenescence in atherosclerosis: A role for chronic viral infections

“…Both immunosenescence and atherosclerosis are multifactorial conditions which share common stimulators, including Ox-LDL ( 111 , 112 ), inflammation ( 113 , 114 ), ROS ( 115 , 116 ), cigarette smoke ( 117 , 118 ), hypertension ( 119 , 120 ), hyperglycaemia ( 121 , 122 ), viral infection ( 123 , 124 ), mitochondrial failure ( 125 , 126 ) and genomic damage ( 127 , 128 ) ( Figure 1 ). Certainly, various drivers of senescence induce SASP secretion and thereby stimulate chronic and low-grade inflammation that participates in atherosclerosis development, and in turn, diverse stimulators of atherosclerosis induce cellular senescence and SASP production.…”

Targeting Molecular Mechanism of Vascular Smooth Muscle Senescence Induced by Angiotensin II, A Potential Therapy via Senolytics and Senomorphics

“…Our understanding of the molecular mechanism leading to senescence is becoming much clearer, particularly those in CVD [7,28,29]. Moreover, genetic or pharmacological removal (senolytics) or prevention (senomorphics) appears to be a powerful tool to investigate contribution of senescence in CVD [29].…”

“…It is important to note that the concept of early vascular aging has been developed to identify an individual with a high CVD risk who has a dissociation between chronological and biological vascular aging [5]. As a major hormone of the renin angiotensin system (RAS), angiotensin II (AngII) has been implicated in induction of premature cellular senescence in vessel wall, thus promoting early vascular aging [6,7].…”