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Published on: October 26, 2020
Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD
Anastasia V Poznyak1, Dwaipayan Bharadwaj2,3, Gauri Prasad3
1Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia.
Insights
The renin-angiotensin-aldosterone system (RAAS) drives atherosclerosis by promoting inflammation and oxidative stress. Targeting RAAS and cytokines offers promising therapeutic strategies for cardiovascular disease (CVD).
Area of Science:
- Cardiovascular Science
- Immunology
- Endocrinology
Background:
- Atherosclerosis, a leading cause of cardiovascular disease (CVD), involves inflammation, lipid alterations, and endothelial injury.
- Current treatments for atherosclerosis and its complications are limited.
- The renin-angiotensin-aldosterone system (RAAS) plays a key role in regulating inflammatory responses and oxidative stress.
Purpose of the Study:
- To review the role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of atherosclerosis.
- To explore RAAS as a potential therapeutic target for atherosclerosis and cardiovascular disease (CVD).
- To summarize current treatment approaches targeting cytokines in CVD.
Main Methods:
- Literature review focusing on the involvement of RAAS in atherosclerosis.
- Analysis of the mechanisms linking RAAS, inflammation, oxidative stress, and endothelial dysfunction.
- Synthesis of data on cytokine-targeting therapies for cardiovascular disease (CVD).
Main Results:
- RAAS activation, particularly via Angiotensin-II, promotes atherogenesis by increasing inflammation and oxidative stress.
- Angiotensin-II stimulates pro-inflammatory cytokines (IL-6, TNF-a, COX-2) and reactive oxygen species (ROS), while reducing nitric oxide (NO) bioavailability.
- Oxidative stress induced by RAAS is a primary driver of endothelial dysfunction, a critical step in atherosclerosis.
Conclusions:
- Components of the RAAS are implicated in multiple facets of atherosclerosis development.
- Targeting RAAS offers a promising strategy for the treatment and prevention of atherosclerosis and associated cardiovascular diseases (CVD).
- Further research into RAAS and cytokine-mediated pathways may yield novel therapeutic interventions.
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.
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