Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review

Abstract

Background: The endothelium plays a pivotal role in homeostatic mechanisms. It specifically modulates vascular tone by releasing vasodilatory mediators, which act on the vascular smooth muscle. Large amounts of work have been dedicated towards identifying mediators of vasodilation and vasoconstriction alongside the deleterious effects of reactive oxygen species on the endothelium. We conducted a systematic review to study the role of the factors released by the endothelium and the effects on the vessels alongside its role in atherosclerosis. Methods: A search was conducted with appropriate search terms. Specific attention was offered to the effects of emerging modulators of endothelial functions focusing the analysis on studies that investigated the role of reactive oxygen species (ROS), perivascular adipose tissue, shear stress, AMP-activated protein kinase, potassium channels, bone morphogenic protein 4, and P2Y2 receptor. Results: 530 citations were reviewed, with 35 studies included in the final systematic review. The endpoints were evaluated in these studies which offered an extensive discussion on emerging modulators of endothelial functions. Specific factors such as reactive oxygen species had deleterious effects, especially in the obese and elderly. Another important finding included the shear stress-induced endothelial nitric oxide (NO), which may delay development of atherosclerosis. Perivascular Adipose Tissue (PVAT) also contributes to reparative measures against atherosclerosis, although this may turn pathological in obese subjects. Some of these factors may be targets for pharmaceutical agents in the near future. Conclusion: The complex role and function of the endothelium is vital for regular homeostasis. Dysregulation may drive atherogenesis; thus, efforts should be placed at considering therapeutic options by targeting some of the factors noted.

Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review

“…The effect of acute hyperglycemia on vascular function remains controversial. Several studies reported that the effect of acute hyperglycemia on endothelial and vascular smooth muscle functions across healthy and cardiometabolic diseased individuals is of relevance [ 1 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ] ( Figure 4 ).…”

“…Although studies on the endothelium function have been performed for more than 30 years, to date, no detailed guidelines on the choice of novel therapeutic and diagnostic targets have been published to deal with the onset of cardiovascular disease. This evidence collides with current clinical practice that demonstrates the important role exhibited by endogenous hyperglycemic hormones in ensuring the proper maintenance of vascular tone under pathological conditions [ 1 , 2 , 3 ]. In these circumstances the role of endothelium-derived relaxing factors is crucial and is mediated by the action of vasodilator prostaglandins, NO, and endothelium-dependent hyperpolarization (EDH) factors, as well as endothelium-derived contracting factors.…”

Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review

“…Although studies on the endothelium function have been performed for more than 30 years, to date, no detailed guidelines on the choice of novel therapeutic and diagnostic targets have been published to attenuate the onset of cardiovascular disease. This evidence collides with current clinical practice that demonstrates an important role exhibited by endogenous hyperglycemic hormones, which are advantageous for ensuring proper maintenance of vascular tone under pathological conditions [1][2][3]. In these circumstances the role of endothelium-derived relaxing factors is crucial and is mediated by the action of vasodilator prostaglandins, NO, and endothelium-dependent hyperpolarization (EDH) factors, as well as endothelium-derived contracting factors.…”

“…In September 2022, PubMed, Ovid's version of MEDLINE, and EM-BASE the systematic review was investigated using the terms "Endothelial vasodilation (5.202 to the present)" "Endothelial vasoconstriction (1.102 to the present)" "nitric oxide inflammation (3,133 to the present)" " nitric oxide diabetes (1,117 to the present) " nitric oxide, "pulmonary hypertension (481 to the present) ", "endothelium-derived relaxing factor inflammation (3,136 to the present)", " endothelium-derived relaxing factor diabetes (1,124 to the present) " and " endothelium-derived relaxing factor pulmonary hypertension (483 to the present) ". The search was directed to the identification of data from basic research articles and randomized controlled trials (RCT).…”

Endothelin-1 as predictor of major adverse cardiovascular events in chronic coronary syndrome patients undergoing coronary intervention

“…4,5 Endothelin-1 is derived from endothelial cells and several studies have reported its associated with endothelial dysfunction. [6][7][8] Endothelial dysfunction has been reported as an atherosclerotic risk factor associated with future cardiovascular events, [9][10][11] and therefore has been considered a pro inflammatory factor [12][13][14] and suggested as a novel prognostic indicator in ACS. However, its role in predicting cardiovascular events in stable coronary artery disease is unclear.…”