Role of miR206 in genistein-induced rescue of pulmonary hypertension in monocrotaline model.
نویسندگان
چکیده
Pulmonary hypertension (PH) is a progressive lung disease associated with proliferation of smooth muscle cells and constriction of lung microvasculature, leading to increased pulmonary arterial pressure, right ventricular failure, and death. We have previously shown that genistein rescues preexisting established PH by significantly improving lung and heart function. (Matori H, Umar S, Nadadur RD, Sharma S, Partow-Navid R, Afkhami M, Amjedi M, Eghbali M. Hypertension 60: 425-430, 2012). Here, we have examined the role of microRNAs (miRs) in the rescue action of genistein in monocrotaline (MCT)-induced PH in rats. Our miR microarray analysis on the lung samples from control, PH, and genistein-rescue group revealed that miR206, which was robustly upregulated to ∼11-fold by PH, was completely normalized to control levels by genistein treatment. Next, we examined whether knockdown of miR206 could reverse preexisting established PH. PH was induced in male rats by 60 mg/kg of MCT, and rats received three intratracheal doses of either miR206 antagomir (10 mg/kg body wt) or scrambled miR control at days 17, 21, and 26. Knockdown of miR206 resulted in significant improvement in the cardiopulmonary function, as right ventricular pressure was significantly reduced to 38.6 ± 3.61 mmHg from 61.2 ± 5.4 mmHg in PH, and right ventricular hypertrophy index was decreased to 0.35 ± 0.04 from 0.59 ± 0.037 in PH. Knockdown of miR206 reversed PH-induced pulmonary vascular remodeling in vivo and was associated with restoration of PH-induced loss of capillaries in the lungs and induction of vascular endothelial growth factor A expression. In conclusion, miR206 antagomir therapy improves cardiopulmonary function and structure and rescues preexisting severe PH in MCT rat model possibly by stimulating angiogenesis in the lung.
منابع مشابه
Role of miR206 in Genistein-Induced Rescue of Pulmonary Hypertension in Monocrotaline
22 Pulmonary hypertension (PH) is a progressive lung disease associated with proliferation of 23 smooth muscle cells and constriction of lung microvasculature leading to increased pulmonary 24 arterial pressure, right ventricular failure and death. We have previously shown that genistein 25 rescues preexisting established PH by significantly improving lung and heart function. Here, we 26 have e...
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متن کاملPulmonary Hypertension Genistein, a Soy Phytoestrogen, Reverses Severe Pulmonary Hypertension and Prevents Right Heart Failure in Rats
Pretreatment with a phytoestrogen genistein has been shown to attenuate the development of pulmonary hypertension (PH). Because PH is not always diagnosed early, we examined whether genistein could also reverse preexisting established PH and prevent associated right heart failure (RHF). PH was induced in male rats by 60 mg/kg of monocrotaline. After 21 days, when PH was well established, rats r...
متن کاملGenistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats.
Pretreatment with a phytoestrogen genistein has been shown to attenuate the development of pulmonary hypertension (PH). Because PH is not always diagnosed early, we examined whether genistein could also reverse preexisting established PH and prevent associated right heart failure (RHF). PH was induced in male rats by 60 mg/kg of monocrotaline. After 21 days, when PH was well established, rats r...
متن کاملGenistein attenuates monocrotaline-induced pulmonary arterial hypertension in rats by activating PI3K/Akt/eNOS signaling.
INTRODUCTION Phytoestrogen genistein may be useful to treat pulmonary arterial hypertension (PAH). However, its mechanism is still not clear. The aim of the present study was to confirm the therapeutic effects of phytoestrogen genistein on PAH in monocrotaline-induced rat model and to explore its mechanism. MATERIALS AND METHODS Sprague-Dawley male rats were randomly divided into 4 groups: co...
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ورودعنوان ژورنال:
- Journal of applied physiology
دوره 119 12 شماره
صفحات -
تاریخ انتشار 2015