Chronic stress and endothelial dysfunction: mechanisms, experimental challenges, and the way ahead

Abstract

<jats:p> Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiologic complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. This review article therefore explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion; 2) discussing mechanistic links between chronic stress and endothelial dysfunction; and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. The data reveal that preclinical models play an important role in our efforts to gain an increased understanding of mechanisms underlying stress-mediated endothelial dysfunction. It is our understanding that this provides a good foundation going forward and we propose that further efforts should be made to a) more clearly define the concept of stress and b) standardize protocols of animal models with specific guidelines to better indicate the mental complications that are simulated. </jats:p>

High Perceived Stress May Shorten Activated Partial Thromboplastin Time and Lead to Worse Clinical Outcomes in Patients With Coronary Heart Disease

“…Although vulnerable plaques are regarded as the culprit factor for a worse cardiac prognosis, “blood prone to thrombosis” has played an important role ( 31 ). Despite the overactivation of the sympathetic nerve system under stress, which might cause the mismatch of oxygen demand and supply for myocardium, mental stress-induced prolonged platelet activation ( 39 , 40 ) and endothelial dysfunction ( 41 ) could be another precipitating factor. With the increased susceptibility of the endothelium to injury, endothelium lesions caused by ischemia or the rupture of plaque, through exposing procoagulant materials to the blood, might catalyze the initialization of thrombosis, and could be further strengthened under the push of high perceived stress through a hypercoagulable state and platelet activation.…”

Impact of Acute and Chronic Psychosocial Stress on Vascular Inflammation

“…Mechanistically, most cytokines upregulate adhesion molecule expression on endothelial cells, a change that subsequently leads to more leukocyte recruitment in the underlying tissue ( 24 , 127 ). Furthermore, systemic activation of the renin/angiotensin/aldosterone system during chronic psychosocial stress may contribute to endothelial dysfunction and cardiovascular inflammation ( 148 ). The renin/angiotensin/aldosterone system involves a multitude of players, such as angiotensin II, that act jointly to regulate fluid balance and blood pressure.…”

Glucocorticoids Promote Extracellular Matrix Component Remodeling by Activating YAP in Human Retinal Capillary Endothelial Cells

“…Systemic GC excess, caused by either Cushing’s syndrome or chronic stress, is associated with some CVDs, such as systemic atherosclerosis, and a large body of evidence supports GC-mediated endothelial dysfunction as a key mechanism in this disease ( De Leo et al, 2010 ; Del Rincón et al, 2014 ; Geer, 2016 ; Sher et al, 2020 ). Atherosclerosis is a disease of large and medium-sized arteries and is the most frequent underlying cause of coronary artery disease, carotid artery disease, and peripheral arterial disease ( Falk, 2006 ).…”