DHT deteriorates the progression of monocrotaline-induced pulmonary arterial hypertension: effects of endogenous and exogenous androgen.
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Le résumé fourni par la source
Pulmonary arterial hypertension (PAH) is more popular among females than males. However, female patients exhibit better prognosis than men, sex hormones may partly explain such sex paradox. Estrogens are disease modifiers in PAH, androgen effects on PAH are yet incompletely characterized. In this study, we sought to determine the effect of androgen depletion and dihydrotestoterone (DHT) repletion on a rat model of monocrotaline-induced PAH (MCT-PH) and to further clarify the possible mechanisms. MCT-PH was induced in male Sprague-Dawley (SD) rats as well as castrated rats with or without concomitant DHT repletion. Our research showed that rats with PAH exhibited cardiopulmonary alterations including induction of right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, right ventricular hypertrophy (RVH) and fibrosis. Moreover, MCT upregulated expression of vascular cell proliferative proteins (PCNA and Ki67), matrix metalloproteinase-2 (MMP-2) and apoptotic proteins (Bax and Bcl-2) in pulmonary artery, and promoted pro-inflammatory cytokines expression (IL-6, TNF-α and IL-1β) and oxidative stress level (SOD activity and MDA level) in perivascular lung tissue. The magnitude of these PAH-induced changes was significantly partly inhibited by castration. DHT replacement reversed castration-action on MCT-related cardiopulmonary alteration. We studied the detrimental effect of endogenous androgen and exogenous DHT in MCT-PH rats, which may be through stimulation of vascular cell proliferation, gelatinolytic activity, apoptosis, perivascular inflammation and oxidative stress.
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Où se fait cette recherche
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Central South University pays non établi dans la noticeUniversité ou école supérieure
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Xiangya Hospital Central South University pays non établi dans la noticeÉtablissement de santé
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Changsha Central Hospital pays non établi dans la noticeÉtablissement de santé
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School of Basic Medicine Department of Cardiology of The 3rd Xiangya Hospital pays non établi dans la noticeUniversité ou école supérieure
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Department of Orthopaedics pays non établi dans la noticeInstitution
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Xiangya School of Pharmaceutical Sciences Department of Pharmacology pays non établi dans la noticeUniversité ou école supérieure
Central South University, Xiangya Hospital Central South University et Changsha Central Hospital, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.