DHT Deteriorates the Progression of Monocrotaline-induced Pulmonary Arterial Hypertension: Effects of Endogenous and Exogenous Androgen

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2019 Oct 22

PMID 31632545

Citations 3

Authors

Juan Wen

Jiajie Wang

Xiaohong Tang

Shangbin Deng

Jia Dai

Xiaohui Li

Weijun Cai

Affiliations

Soon will be listed here.

Abstract

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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