Expert opinion on therapeutic targets · 2010
Correlation between plasma levels of apelin and myocardial hypertrophy in rats and humans: possible target for treatment?
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Falcão-Pires Inês, Gonçalves Nádia, Gavina Cristina, Pinho Sónia, Teixeira Tânia, Moura Cláudia, Amorim Mário Jorge, Pinho Paulo, Areias José Carlos, Leite-Moreira Adelino
Аннотация
OBJECTIVE: To investigate the effects of left ventricular (LV) pressure overload and diabetes on the apelinergic system.
RESEARCH DESIGN/METHODS: Pressure overload was established in rats by supra-renal aortic-banding. Six weeks later, diabetes was induced by streptozotocin (65 mg/kg, intraperitoneal), resulting in four groups: sham, banded (BA), diabetic (DM) and diabetic-banded (DM-BA). Twelve weeks later, LV function and structure were evaluated by echocardiography and biopsies and plasma samples collected. Furthermore, plasma samples and LV-endomyocardial biopsies were procured from aortic stenosis and mitral stenosis patients during surgery to evaluate myocardial expression of apelin and APJ-receptor and plasma levels of apelin.
RESULTS: Direct correlations between apelin plasma levels and LV-mass index and between apelin and APJ myocardial expression were observed both in humans and rats. Expression of apelin and APJ was not significantly altered by pressure-overload in humans, being downregulated by pressure overload and even more by diabetes in rats. Finally, an inverse correlation between apelin rat plasma levels and its myocardial expression was observed.
CONCLUSIONS: While apelin/APJ myocardial expression decreases, apelin plasma levels increase in LV hypertrophy. Considering apelin's positive inotropic and vasodilator properties, this elevation in apelin plasma levels may represent a compensatory mechanism to maintain inotropism and cardiac output during pressure-overload or diabetic cardiomyopathy.
RESEARCH DESIGN/METHODS: Pressure overload was established in rats by supra-renal aortic-banding. Six weeks later, diabetes was induced by streptozotocin (65 mg/kg, intraperitoneal), resulting in four groups: sham, banded (BA), diabetic (DM) and diabetic-banded (DM-BA). Twelve weeks later, LV function and structure were evaluated by echocardiography and biopsies and plasma samples collected. Furthermore, plasma samples and LV-endomyocardial biopsies were procured from aortic stenosis and mitral stenosis patients during surgery to evaluate myocardial expression of apelin and APJ-receptor and plasma levels of apelin.
RESULTS: Direct correlations between apelin plasma levels and LV-mass index and between apelin and APJ myocardial expression were observed both in humans and rats. Expression of apelin and APJ was not significantly altered by pressure-overload in humans, being downregulated by pressure overload and even more by diabetes in rats. Finally, an inverse correlation between apelin rat plasma levels and its myocardial expression was observed.
CONCLUSIONS: While apelin/APJ myocardial expression decreases, apelin plasma levels increase in LV hypertrophy. Considering apelin's positive inotropic and vasodilator properties, this elevation in apelin plasma levels may represent a compensatory mechanism to maintain inotropism and cardiac output during pressure-overload or diabetic cardiomyopathy.
Предметные рубрики MeSH
AgedAnimalsAortic Valve StenosisApelinApelin ReceptorsCardiomegalyCarrier ProteinsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2EchocardiographyFemaleGene Expression RegulationHumansIntercellular Signaling Peptides and ProteinsMaleMitral Valve StenosisRatsRats, WistarReceptors, G-Protein-CoupledVentricular Pressure