Simvastatin protects against the development of monocrotaline-induced pulmonary hypertension in rats via a heme oxygenase-1–dependent pathway

Autor:	Yun-jian Zhang, Bing-xiang Yu, Wei-Hua Zhang, Chun-ping Liu, Wei-xuan Lu
Rok vydání:	2011
Předmět:	Pulmonary and Respiratory Medicine Simvastatin medicine.medical_specialty Hypertension Pulmonary Clinical Biochemistry Protoporphyrins Hemodynamics Vasodilation Pharmacology Muscle hypertrophy Rats Sprague-Dawley chemistry.chemical_compound Internal medicine polycyclic compounds medicine Animals Enzyme Inhibitors Lung Molecular Biology Heme Monocrotaline Hypertrophy Right Ventricular Interleukin-6 business.industry medicine.disease Pulmonary hypertension Rats Heme oxygenase Arterioles Endocrinology medicine.anatomical_structure chemistry Heme Oxygenase (Decyclizing) Hydroxymethylglutaryl-CoA Reductase Inhibitors business Signal Transduction medicine.drug
Zdroj:	Experimental Lung Research. 37:492-499
ISSN:	1521-0499 0190-2148
DOI:	10.3109/01902148.2011.591892
Popis:	Heme oxygease-1 (HO-1) is the rate-limiting enzyme in heme catabolism. Induction of HO-1 has been shown to have vasodilatory, anti-inflammatory, and proapoptotic effects. More recently, experimental studies suggested the potential of simvastatin as a novel therapy for pulmonary hypertension (PH); however, the underlying mechanism remains to be investigated. The aim of this study was to evaluate whether HO-1 is required for the pulmonary vascular protective effects of simvastatin. Simvastatin (2 mg/kg/day) was administered once daily to rats for 4 weeks after monocrotaline (MCT) injection. Zn-protoporphyrin (Znpp), a potent inhibitor of HO, was used to confirm the role of HO-1. The hemodynamic changes, right heart hypertrophy, interleukin-6 (IL-6) level, and HO-1 protein expression in lungs were measured at day 28. Simvastatin significantly ameliorated mean pulmonary arterial hypertension (20.6 mm Hg). In addition, perivascular infiltration of inflammatory cells and the level of IL-6 were decreased in simvastatin treatment group. Simvastatin also increased significantly lung HO-1 protein expression. Inhibiting HO-1 using Znpp resulted in a loss of the effect of simvastatin in MCT rats. These results suggest that HO-1 expression is critical for the vascular protective effects of simvastatin in MCT-induced PH rats.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1131d9f5dbfe1bba57f8fc7a30b753f5 https://doi.org/10.3109/01902148.2011.591892 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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