RESOLVIN-D1 PREVENTS ANGIOTENSIN II-INDUCED CARDIAC REMODELING AND HYPERTENSION THROUGH HEART INFLAMMATION ATTENUATION
SUMMARY Introduction: Despite the pharmacological arsenal available to treat hypertension (HBP), chronic patients may develop irreversible cardiac remodeling and fibrosis. Among the triggers of HBP are metabolic diseases, cellular aging and hormonal dysregulation. In the latter context, Angiotensin...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | Chile |
| OAI Identifier: | oai:repositorio.anid.cl:10533/252932 |
| Acceso en línea: | https://hdl.handle.net/10533/252932 |
| Access Level: | acceso abierto |
| Palabra clave: | Medicina y Ciencias de la Salud Ciencias de la Salud Farmacología y Farmacia |
| Sumario: | SUMMARY Introduction: Despite the pharmacological arsenal available to treat hypertension (HBP), chronic patients may develop irreversible cardiac remodeling and fibrosis. Among the triggers of HBP are metabolic diseases, cellular aging and hormonal dysregulation. In the latter context, Angiotensin II (Ang II) regulates the hemodynamics of the circulatory system, maintaining the volume and homeostasis of the cardiovascular system. However, chronic and exacerbated Ang II activity results in inflammation in blood vessels and heart tissue, increased preload, blood pressure, and cardiac remodeling, leading to irreversible heart failure. Resolvin-D1 (RvD1) belongs to the family of autacoid lipids with potent anti-inflammatory and pro-resolution effects in diverse in vitro and in vivo cardiovascular pathological models, such as myocardial infarction, ischemia/reperfusion and aortic stenosis, preventing the recruitment of leukocytes, expression of inflammation markers and cardiac fibrosis. However, to date no studies have yet been conducted evaluating the protective effects of RvD1 against chronic damage caused by HBP. Hence, we set out to evaluate such effects in an Ang II infusion HBP model. Methods: Ang-II (Ang II, 1.5 mg/kg/day) was infused into male C57BL/6 mice via Alzet® mini osmotic pumps for 7 or 14 days, along with the administration of Resolvin-D1 (RvD1, 3 µg/kg/day, ip) one day after surgery and during the infusion period. Blood pressure and functional parameters were evaluated by echocardiography. At the end of the experimental periods, tissues were harvested and histological parameters were studied by immunohistochemistry and plasma cytokines using LUMINEX. Results: RvD1 decreased the cardiac infiltration of neutrophils and granulation tissue formation induced by Ang II at 7 and 14 days; the expression of cardiac ICAM-1 and VCAM-1; the increase in plasmatic levels of IL-1β, TNF-α, IL-6, KC, MCP-1 while IL-10 was increased at both times of infusion. In addition, RvD1 was able to prevent left ventricular and cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, and systolic and diastolic hypertension. In summary, this study reveals new cardioprotective effects of RvD1 on Ang II-induced hypertension and cardiac remodeling, providing novel information on a possible therapeutic application. |
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