Resolvin D2 Attenuates Cardiovascular Damage in Angiotensin II-Induced Hypertension

Abstract

BACKGROUND: Resolution of inflammation is orchestrated by specialized pro-resolving mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension. METHODS: Aorta, small mesenteric arteries, heart, and peritoneal macrophages were taken from C57BL/6J mice, infused or not with Angiotensin II (AngII 1.44 mg/kg/day, 14 days) in presence or absence of RvD2 (100 ng/mice, every second day) starting 1 day before or 7 days after AngII infusion. RESULTS: Enzymes and receptors involved in SPMs biosynthesis and signaling were increased in aorta or heart from AngII-infused mice. We also observed a differential regulation of SPMs in heart from these mice. Preventive treatment with RvD2 partially avoided AngII-induced hypertension and protected the heart and large and small vessels against functional and structural alterations induced by AngII. RvD2 increased the availability of vasoprotective factors, modified SPMs profile, decreased cardiovascular fibrosis, and increased the infiltration of pro-resolving macrophages. When administered in hypertensive animals with established cardiovascular damage, RvD2 partially improved cardiovascular function and structure, decreased fibrosis, reduced the infiltration of neutrophils, and shifted macrophage phenotype toward a pro-resolving phenotype. CONCLUSIONS: There is a disbalance between proinflammatory and resolution mediators in hypertension. RvD2 protects cardiovascular function and structure when administered before and after the development of hypertension by modulating vascular factors, fibrosis and inflammation. Activating resolution mechanisms by treatment with RvD2 may represent a novel therapeutic strategy for the treatment of hypertensive cardiovascular disease.

The Melatonin Derivative ITH13001 Prevents Hypertension and Cardiovascular Alterations in Angiotensin II-Infused Mice

“…Left ventricular hypertrophy, characterized by cardiomyocyte hypertrophy and cardiac fibrosis, is one of the main hallmarks of hypertensive heart disease (Susic and Frohlich, 2000). Accordingly, AngII-infused mice exhibited left ventricular hypertrophy and increased cardiomyocyte area and fibrotic markers collagen I and Bnp levels, as previously described (Díaz del Campo et al, 2023). ITH13001 treatment prevented these effects, suggesting an amelioration of hypertensive heart disease; these results agree with the protective effects on cardiac remodelling of antioxidants such as Mito-TEMPO, Mitoquinone, sulforaphane, allicin and N-acetylcysteine in animal models of cardiovascular pathologies (Lombardi al., 2009;Li et al, 2012;Martínez-Revelles et al, 2013; Goh et al, 2019;Ramachandra et al, 2021;Su et al, 2021).…”

Resolvin D1 attenuates Ang II-induced hypertension in mice by inhibiting the proliferation, migration and phenotypic transformation of vascular smooth muscle cells by blocking the RhoA/mitogen-activated protein kinase pathway

“…Previous studies have shown that there is an imbalance between proinflammatory and resolution mediators in hypertension, and low SPM levels may be an indicator of the development of hypertension [ 32 , 33 ]. Resolvin D2 has been proven to improve Ang II-induced hypertension by modulating vascular factors, fibrosis and inflammation to protect cardiovascular structure and function [ 33 ]. RvD1 also plays a cardioprotective role in angiotensin II-induced hypertension and cardiac remodeling, but the mechanism by which RvD1 improves hypertension is unclear [ 9 ].…”

Uncovering the Power of GPR18 Signalling: How RvD2 and Other Ligands Could Have the Potential to Modulate and Resolve Inflammation in Various Health Disorders

“…Cardiovascular disorders, including hypertension, are associated with vascular damage, endothelium dysfunction, adventitial fibrosis, and inflammation. An interesting methodological solution was presented by the Briones research group, which studied two different groups of mice with hypertension: first, a prevention group in which angiotensin II (AngII)-infused mice were treated with RvD2 (100 ng/mouse) one day before AngII infusion and throughout the experiment (every two days); second, an intervention group in which RvD2 was given at day seven after AngII infusion till the end of the experiment [ 56 ]. They proved that administration of RvD2 to hypertensive mice prevented and reduced changes in cardiovascular function, remodelling, fibrosis, immune cell infiltration, and inflammation.…”