Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD

Abstract

Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.

Evaluation of the value of conventional and unconventional lipid parameters for predicting the risk of diabetes in a non-diabetic population

“…The imbalance between renin and angiotensin II can lead to a large number of chronic and acute diseases [ 64 , 65 ], and plaque formation induced by angiotensin II in the early stage is one of the most important effects of RAAS on atherosclerosis [ 66 ], while under pathological conditions, RAAS also contributes directly or indirectly to the development of atherosclerosis and its various complications through its effects on other systems [ 67 ]. In addition to this, when renin and angiotensin II are imbalanced, the RAAS detrimental axis will also increase the release of inflammatory cytokines, and generate and increase oxidative stress; these pathological changes will further promote the formation of atherosclerosis, exacerbated IR, and decreased insulin secretion [ 66 , 68 ]. On the other hand, it should also be noted that serum hepcidin and hepcidin/ferritin ratio also play an important role in the development of IR and diabetes [ 69 , 70 ].…”

Alamandine alleviated heart failure and fibrosis in myocardial infarction mice

“…The understanding of the balance between the two branches of RAS under different physiopathological conditions furnish novel therapeutic targets that may mitigate the development of CVDs [ 86 ]. Previous studies have confirmed the cardioprotective effects of ACE2 activators and ACE inhibitors (ACEIs) against MI-induced cardiac injure [ 87 – 90 ].…”

Gene Expression Profiling of Markers of Inflammation, Angiogenesis, Coagulation and Fibrinolysis in Patients with Coronary Artery Disease with Very High Lipoprotein(a) Levels Treated with PCSK9 Inhibitors

“…However, we must be aware that in addition to statins, all of our patients have been treated for more than six months also with ACE inhibitors/sartans, β blockers, and acetylsalicylic acid. The effect on the parameters of inflammation is well-recognized for statins [ 16 , 17 ], ACE inhibitors/sartans [ 29 ], β blockers [ 30 ], and acetylsalicylic acid [ 31 ], while all of them except β blockers also affect coagulation and fibrinolysis [ 16 , 17 , 29 , 31 ]. The inflammatory cytokine IL-1β stimulates the endothelial cells and leukocytes to produce intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) [ 6 ].…”