The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

Abstract

The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

“…Such nitrovasodilators consist of metabolic donors (organic nitrates and nitrites, nicorandil) and direct donors (sodium nitroprusside (SNP), NO gas and molsidomine) [49]. Moreover, NO may also interfere with β-blockers and with the renin-angiotensinaldosterone system (RAAS) [34,41].…”

“…In turn, it may result in the development of hypertension, CHF, stroke or renal disease. The RAAS has also pro-inflammatory and profibrotic effects at the cellular and molecular levels [29,41]. What is more, the activation of the RAAS results in the subsequent activation of angiotensin II which markedly can induce both O 2¯ and NO formulation.…”

Leukocyte RhoA exchange factor Arhgef1 mediates vascular inflammation and atherosclerosis

“…Consequently, AT1 receptor activation in both arterial wall (smooth muscle and endothelial) and circulating (leukocytes and platelets) cells leads to pleiotropic actions affecting arterial contraction, vascular permeability, hemostasis, immune/inflammatory cell activation, and oxidative stress (3). Pharmacological inhibition or genetic disruption of the RAAS decreases atherosclerosis in various experimental models (4)(5)(6)(7)(8)(9)(10)(11), and clinical trials support this pro-atherosclerotic and proinflammatory role of Ang II in humans (12,13). However, the respective contribution of leukocytes and arterial wall cells in the effect of Ang II on inflammation and atherosclerosis is still not clearly established, and the intracellular signaling pathways involved remained largely unknown.…”

Comparison of Hibiscus sabdariffa L. Extract and Enalapril with Regard to Their Effect on Lung Fibrosis in a Bleomycin-induced Rat Model of Lung Fibrosis

“…Although the main function of the renin angiotensin system and its effectors is blood pressure regulation, it plays a key role in promoting inflammatory cascades. Inflammation is a crucial mechanism in the progression and development of fibrotic processes, and the rennin-angiotensin system has profibrotic and proinflammatory effects at the cellular and molecular levels (9). During the experimental lung injury, ACE inhibitors were found to attenuate the activation of tumor necrosis factor (TNF) and endothelial cells and the deposition of collagen proteins, possibly by decreasing the apoptosis rate of epithelial cells (8).…”