Correlation between plasma levels of apelin and myocardial hypertrophy in rats and humans: possible target for treatment?
OBJECTIVE
To investigate the effects of left ventricular (LV) pressure overload and diabetes on the apelinergic system.


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.
Falcão-Pires
Inês
I
University of Porto, Department of Physiology, Cardiovascular R&D Unit, Faculty of Medicine, 4200-319 Porto, Portugal.
Gonçalves
Nádia
N
Gavina
Cristina
C
Pinho
Sónia
S
Teixeira
Tânia
T
Moura
Cláudia
C
Amorim
Mário Jorge
MJ
Pinho
Paulo
P
Areias
José Carlos
JC
Leite-Moreira
Adelino
A
D000368:Aged; D000818:Animals; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D000073861:Apelin; D000075244:Apelin Receptors; D006332:Cardiomegaly / Q000503:physiopathology*; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D004452:Echocardiography; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D008297:Male; D008946:Mitral Valve Stenosis / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D017725:Ventricular Pressure
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled