Antioxidant-based therapies for angiotensin II-associated cardiovascular diseases

Abstract

Cardiovascular diseases, including hypertension and heart failure, are associated with activation of the renin-angiotensin system (RAS) and increased circulating and tissue levels of ANG II, a primary effector peptide of the RAS. Through its actions on various cell types and organ systems, ANG II contributes to the pathogenesis of cardiovascular diseases by inducing cardiac and vascular hypertrophy, vasoconstriction, sodium and water reabsorption in kidneys, sympathoexcitation, and activation of the immune system. Cardiovascular research over the past 15-20 years has clearly implicated an important role for elevated levels of reactive oxygen species (ROS) in mediating these pathophysiological actions of ANG II. As such, the use of antioxidants, to reduce the elevated levels of ROS, as potential therapies for various ANG II-associated cardiovascular diseases has been intensely investigated. Although some antioxidant-based therapies have shown therapeutic impact in animal models of cardiovascular disease and in human patients, others have failed. In this review, we discuss the benefits and limitations of recent strategies, including gene therapy, dietary sources, low-molecular-weight free radical scavengers, polyethylene glycol conjugation, and nanomedicine-based technologies, which are designed to deliver antioxidants for the improved treatment of cardiovascular diseases. Although much work has been completed, additional research focusing on developing specific antioxidant molecules or proteins and identifying the ideal in vivo delivery system for such antioxidants is necessary before the use of antioxidant-based therapies for cardiovascular diseases become a clinical reality.

Epigallocatechin-3-Gallate Ameliorates Angiotensin II-Induced Oxidative Stress and Apoptosis in Human Umbilical Vein Endothelial Cells through the Activation of Nrf2/Caspase-3 Signaling

“…Ang II is a crucial factor responsible for hypertension and cardiovascular disease [6,26]. Recently, some studies have focused on exploring the effect of Ang II on endothelial cells [27,28,29,30].…”

“…Angiotensin II (Ang II) is a key independent risk factor of hypertension, inducing cardiovascular disease development [5,6]. Many reports have suggested that Ang II stimulates nicotinamide adenine dinucleotide phosphate generation in the vascular cell.…”

Angiotensin II increases secreted frizzled-related protein 5 (sFRP5) expression through AT1 receptor/Rho/ROCK1/JNK signaling in cardiomyocytes

“…Angiotensin (Ang) II, an important mediator of the renin-angiotensin system (RAS), directly promotes myocardial hypertrophy, hypertension, and interstitial fibrosis [2]. There are two Ang II receptor subtypes: angiotensin II type 1 receptor (AT1-R) and angiotensin II type 2 receptor (AT2-R).…”

Protective Effect of a Fish Egg Homogenate Marine Compound on Arterial Ultrastructure in Spontaneous Hypertensive Rats

“…4 However, the use of anti-oxidants as a therapeutic/preventive tool is still debated. 5,6 In addition, a predisposing factor for atherosclerosis is most definitively regarded to be a hypertensive state. 7 Given the uniqueness of the composition of sturgeon eggs as compared to other marine species regarding polyunsaturated fatty acids (PUFAs) and phospholipid moieties, 8 and in consideration of our recent work proving the efficacy of a controlled caviar-derived homogenate, LD-1227 (Caviarlieri, LabDom, Switzerland), as an anti-oxidant/antiinflammatory modulator with a wider efficacy properties as compared to docosahexaenoic acid (DHA), 9,10 we also tested this compound on the ultrastructure of the SHR aorta.…”