Dataset Information

Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats.

ABSTRACT: AIMS:GPR30 is a novel oestrogen receptor expressed in various tissues, including the heart. We determined the role of GPR30 in the maintenance of left ventricular (LV) structure and diastolic function after the surgical loss of ovarian hormones in the female mRen2.Lewis rat, a model emulating the cardiac phenotype of the post-menopausal woman. METHODS AND RESULTS:Bilateral oophorectomy (OVX) or sham surgery was performed in study rats; the selective GPR30 agonist, G-1 (50 µg/kg/day), or vehicle was given subcutaneously to OVX rats from 13-15 weeks of age. Similar to the cardiac phenotype of sham rats, G-1 preserved diastolic function and structure relative to vehicle-treated OVX littermates independent of changes in blood pressure. G-1 limited the OVX-induced increase in LV filling pressure, LV mass, wall thickness, interstitial collagen deposition, atrial natriuretic factor and brain natriuretic peptide mRNA levels, and cardiac NAD(P)H oxidase 4 (NOX4) expression. In vitro studies showed that G-1 inhibited angiotensin II-induced hypertrophy in H9c2 cardiomyocytes, evidenced by reductions in cell size, protein content per cell, and atrial natriuretic factor mRNA levels. The GPR30 antagonist, G15, inhibited the protective effects of both oestradiol and G-1 on this hypertrophy. CONCLUSION:These data show that the GPR30 agonist G-1 mitigates the adverse effects of oestrogen loss on LV remodelling and the development of diastolic dysfunction in the study rats. This expands our knowledge of the sex-specific mechanisms underlying diastolic dysfunction and provides a potential therapeutic target for reducing the progression of this cardiovascular disease process in post-menopausal women.

SUBMITTER: Wang H

PROVIDER: S-EPMC3307382 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats.

Wang Hao H Jessup Jewell A JA Lin Marina S MS Chagas Clarissa C Lindsey Sarah H SH Groban Leanne L

Cardiovascular research 20120210 1

<h4>Aims</h4>GPR30 is a novel oestrogen receptor expressed in various tissues, including the heart. We determined the role of GPR30 in the maintenance of left ventricular (LV) structure and diastolic function after the surgical loss of ovarian hormones in the female mRen2.Lewis rat, a model emulating the cardiac phenotype of the post-menopausal woman.<h4>Methods and results</h4>Bilateral oophorectomy (OVX) or sham surgery was performed in study rats; the selective GPR30 agonist, G-1 (50 µg/kg/da ...[more]

PMID: 22328091

Similar Datasets

Project description:PurposeTo assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.Materials and methodsSeventy-seven patients were examined using DSCT and Doppler echocardiography on the same day. Reservoir, conduit, and contractile function of LA were evaluated by measuring LA volume (LAV) during different cardiac phases and all parameters were normalized to body surface area (BSA). Patients were divided into four groups (normal, impaired relaxation, pseudonormal, and restrictive LV diastolic filling) according to echocardiographic findings. The LA phasic volume and function in different stages of LV diastolic function was compared using one-way ANOVA analysis. The correlations between indexed volume of LA (LAVi) and diastolic function in different stages of LV were evaluated using Spearman correlation analysis.ResultsLA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001), minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased.ConclusionsLA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function.

Dataset Information

Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats.

Publications

Activation of GPR30 attenuates diastolic dysfunction and left ventricle remodelling in oophorectomized mRen2.Lewis rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets