Proinflammatory Role of Angiotensin II in the Aorta of Normotensive Mice

Abstract

Angiotensin II plays important functions in cardiovascular system mediating actions leading to inflammatory responses such as activation of VSMC in order to produce ROS, inflammatory cytokines, chemokines, and adhesion molecules. Changes in angiotensin II production could stimulate the recruitment and activation of myeloid cells initiating local inflammatory response without effect on BP. We aimed to verify if angiotensin II induces an inflammatory response in the aorta and if it correlates with variations in BP. C57Bl/6 mice treated with saline solution (0.9%, control group) or angiotensin II (30ng/kg, Ang II group) were used. BP and HR levels were measured. Immunohistochemistry for IL1-β, TGF-β, iNOS, CD45, andα-actin was performed in the aorta. BP and HR do not change. A biphasic response was observed both for IL1-βand TGF-βexpression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and a second increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (48 hours) in tunica adventitia. Immunoblotting toα-actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic VSMCs phenotype. The results suggest that angiotensin II, even at doses that do not alter BP, induces the expression of inflammatory markers and migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may increase the propensity to develop a cardiovascular injury, even in normotensive individuals.

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

“…In addition to this, Ang II has also been shown to have important oxidative, inflammatory, and immune-mediated actions. Ang II even at doses that do not alter blood pressure, allows the migration of inflammatory cells and induces the expression of inflammatory markers in the aorta of normotensive mice ( Lima et al, 2019 )…”

“…In addition to this, Ang II has also been shown to have important oxidative, inflammatory, and immune-mediated actions. Ang II even at doses that do not alter blood pressure, allows the migration of inflammatory cells and induces the expression of inflammatory markers in the aorta of normotensive mice (Lima et al, 2019) Nair et al in 2015 found toll-like receptor 4 (TLR4), highmobility group box 1 (HMGB1), and proinflammatory cytokines mediated immune response contributed to Ang II-induced hypertension in rat tubular epithelial cell line NRK52E . In support of this concept, they designed another study to determine the involvement of HMGB1 signaling in Ang II-induced hypertension in the para ventricular nucleus (PVN).…”

Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries

“…On the other hand, the physiology and morphology of PVAT are influenced by inflammatory cytokines, the sympathetic nervous system, and vasoactive peptides [20,[22][23][24]. Despite a growing evidence of the vital role of normal PVAT in maintaining a healthy structure of the arterial wall and a www.bjbms.org Ruda Zorc-Pleskovič, et al: Influence of inflammatory cells in perivascular adipose tissue on the media detrimental effect of diseased PVAT on the development of atherosclerosis, the interplay of all the factors remains to be adequately understood.…”

Exploring the Relationship of Perivascular Adipose Tissue Inflammation and the Development of Vascular Pathologies

“…The components of the renin angiotensin aldosterone system are expressed in PVAT. Its bioactive peptide, angiotensin II (Ang II), exerts its inflammatory effect by stimulating the expression of adhesion molecules and cytokines such as MCP-1 and IL-6 [ 58 ]. Ang II is also reported to induce immune cells including T lymphocytes, M1 and M2 macrophages, and dendritic cell infiltration in PVAT [ 59 , 60 ].…”