Resolvin-D1 attenuation of angiotensin II-induced cardiac inflammation in mice is associated with prevention of cardiac remodeling and hypertension

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1867

Article

Olivares-Silva, Francisco^1,2,3  De Gregorio, Nicole^2,3  Espitia-Corredor, Jenaro^1,4,5  Espinoza, Claudio¹  Vivar, Raul⁶  Silva, David^2,3  Osorio, Jose Miguel¹  Lavandero, Sergio^2,3,7  Peiro, Concepcion^4,5  Sanchez-Ferrer, Carlos^4,5  Diaz-Araya, Guillermo^1,2,3 

[1] Univ Chile, Fac Chem & Pharmaceut Sci, Dept Chem Pharmacol & Toxicol, Santiago, Chile

[2] Univ Chile, Adv Ctr Chron Dis ACCDiS, Fac Chem & Pharmaceut Sci, Santiago, Chile

[3] Univ Chile, Fac Med, Santiago, Chile

[4] Univ Autonoma Madrid, Dept Pharmacol, Fac Med, Madrid, Spain

[5] Hosp Univ La Paz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain

[6] Univ Chile, Fac Med, Biomed Sci Inst, Pharmacol Program, Santiago, Chile

[7] Univ Texas Southwestern Med Ctr Dallas, Cardiol Div, Dept Internal Med, Dallas, TX 75390 USA

关键词: Resolvin-D1;    Angiotensin II;    Cardiac remodeling;    Hypertension;    Inflammation;   

DOI  :  10.1016/j.bbadis.2021.166241

来源: Elsevier

【 摘 要 】

Aims: Despite the broad pharmacological arsenal to treat hypertension, chronic patients may develop irreversible cardiac remodeling and fibrosis. Angiotensin II, the main peptide responsible for the Renin-AngiotensinAldosterone-System, has been closely linked to cardiac remodeling, hypertrophy, fibrosis, and hypertension, and some of these effects are induced by inflammatory mediators. Resolvin-D1 (RvD1) elicits potent anti-inflammatory and pro-resolving effects in various pathological models. In this study, we aimed to examine whether RvD1 ameliorates cardiac remodeling and hypertension triggered by angiotensin II. Methods and results: Alzet (R) osmotic mini-pumps filled with angiotensin II (1.5 mg/kg/day) were implanted in male C57BL/6 J mice for 7 or 14 days. RvD1 (3 mu g/kg/day, i.p) was administered one day after the surgery and during the complete infusion period. Blood pressure and myocardial functional parameters were assessed by echocardiography. At the end of the experimental procedure, blood and heart tissue were harvested, and plasma and histological parameters were studied. After 7 and 14 days, RvD1 reduced the increase of neutrophil and macrophage infiltration triggered by angiotensin II, and also reduced ICAM-1 and VCAM-1 expression levels. RvD1 also reduced cytokine plasma levels (IL-1 beta, TNF-alpha, IL-6, KC, MCP-1), cardiac hypertrophy, interstitial and perivascular fibrosis, and hypertension. Conclusions: This study unveils novel cardioprotective effects of RvD1 in angiotensin II-induced hypertension and cardiac remodeling by attenuating inflammation and provides insights into a potential clinical application.

【 授权许可】

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