Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility

Szokodi, István; Tavi, Pasi; Földes, Gábor; Voutilainen-Myllylä, Sari; Ilves, Mika; Tokola, Heikki; Pikkarainen, Sampsa; Piuhola, Jarkko; Rysä, Jaana; Tóth, Miklós; Ruskoaho, Heikki

doi:10.1161/01.res.0000033522.37861.69

Cited by 561 publications

(549 citation statements)

References 47 publications

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“…Apelin has been shown to exert potent positive inotropic effect on normal and failing myocardium. 25,26 Furthermore, apelin has cardioprotective effects against ischemia and reperfusion injury in rats. 27 Several others adipokines have been identified, but whether these modulate cardiac function is not clear so far.…”

Section: Role Of Adipose Tissue In Cardiac Dysfunction C Look Et Almentioning

confidence: 99%

Adipocyte-derived factors suppress heart contraction

et al. 2010

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Background: Obesity is strongly associated with cardiovascular diseases including systemic hypertension, coronary artery disease and heart failure. Despite several investigations the pathophysiological mechanisms involved remain unclear. We have previously shown that adipose tissue exerts a highly potent activity with an acute depressant effect on cardiomyocytes, thus suggesting direct involvement of adipose tissue in the development of heart dysfunction. Objective and Design: This study investigates the effects of adipocyte factors obtained from subcutaneous adipose tissue on the whole cardiac function by using isolated perfused rat hearts in a Langendorff mode. We recorded changes in coronary flow, developed isovolumetric left ventricular pressure, contraction rate and relaxation rate. Results: We observed a significant decrease in heart contractility parameters as well as in coronary flow within a few seconds of incubation with adipocyte factors. The cardiodepressant effects could not be blocked by the nonselective cyclooxygenase-inhibitor indomethacin. Human adipocytes release tumor necrosis factor-a, interleukin-6 (IL-6) and IL-1b into extracellular medium. These cytokines were tested for their potential effect but were, however, not responsible for the cardiodepressant effect observed. Conclusion: These data indicate that human adipocytes secrete factors with a strong acute depressant effect on cardiac force generation and coronary flow due to contraction of the coronary vessels, thus suggesting a direct role of adipose tissue in the pathogenesis of cardiac dysfunction.

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Section: Role Of Adipose Tissue In Cardiac Dysfunction C Look Et Almentioning

confidence: 99%

Adipocyte-derived factors suppress heart contraction

et al. 2010

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“…Functionally, actions of apelin start to emerge as evident in experimental studies (for a review see 3). For example, apelin has been shown to exert cardiovascular effects including positive inotropic action and to reduce blood pressure, as demonstrated in rodents (3,15,16). Apelin also increases drinking behavior (14) and reduces food intake (17) in model experiments in rodents.…”

Section: Introductionmentioning

confidence: 98%

The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice

Winzell

Magnusson

Åhrén

2005

Regulatory Peptides

177

114

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Apelin is the endogenous ligand of the G-protein coupled apj receptor. Apelin is expressed in the brain, the hypothalamus and the stomach and was recently shown also to be an adipokine secreted from the adipocytes. Although apelin has been suggested to be involved in the regulation of food intake, it is not known whether the peptide affects islet function and glucose homeostasis. We show here that the apj receptor is expressed in pancreatic islets and that intravenous administration of full-length apelin-36 (2 nmol/kg) inhibits the rapid insulin response to intravenous glucose (1g/kg) by 35% in C57BL/6J mice. Thus, the acute (1-5 min) insulin response to intravenous glucose was 682±23 pmol/l after glucose alone (n=17) and 445±58 pmol/l after glucose plus apelin-36 (n=18; P=0.017). This was associated with impaired glucose elimination (the 5-20 min glucose elimination was 2.9±0.1%/min after glucose alone versus 2.3±0.2%/min after glucose plus apelin-36, P=0.008). Apelin (2nmol/kg) also inhibited the insulin response to intravenous glucose in obese insulin resistant high-fat fed C57BL/6J mice (P=0.041). After 60 min incubation of isolated islets from normal mice, insulin secretion in the presence of 16.7 mmol/l glucose was inhibited by apelin-36 at 1 µmol/l, whereas apelin-36 did not significantly affect insulin secretion at 2.8 or 8.3 mmol/l glucose or after stimulation of insulin secretion by KCl. Islet glucose oxidation at 16.7 mmol/l was not affected by apelin-36. We conclude that the apj receptor is expressed in pancreatic islets and that apelin-36 inhibits glucose-stimulated insulin secretion both in vivo and in vitro.This may suggest that the islet beta-cells are targets for apelin-36.

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“…Although apelin is also synthesized in the adipose tissue and was listed as adipocytokine and studied as one [8][9][10][11], its major site of synthesis and target is the endothelium and the cardiovascular system. It is the most potent endogenic positive inotropic agent and is a positive regulator of angiotensin converting enzyme type 2, and so it is a RAAS antagonist [12,13]. Experimental studies conducted so far have attributed apelin a protective role on the cardiovascular system, but also on the nervous system, liver, pancreas and kidneys [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Serum level of apelin-13 negatively correlated with NT-proBNP in heart failure patients

Goidescu

Anton

Leucuţa

et al. 2016

Revista Romana De Medicina De Laborator

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Background: Apelin is a potent endogenous inotropic peptide with a major role in counteracting the aldosterone and angiotensin II and their negative effects on the cardiovascular system. The exact role of apelin in the pathophysiology of this disease is not well understood. We aimed to investigate the possible associations of apelin-13with clinical and paraclinical characteristics in HF patients as well as studying its dynamics during the course of the heart failure. Method: We performed a prospective observational cohort single-center study. We compared the baseline serum levels of apelin-13 and NT-proBNP level in 53 heart failure patients (acute heart failure, chronic compensated heart failure and chronic decompensated heart failure). We divided the patients according to the apelin-13 level: above and below the median, and we analyzed the relationship between serum apelin-13 and the clinical, echocardiographic, electrocardiographic and biological parameters. Twenty patients were followed-up (after an average time interval of 9 months), investigating the same parameters. Results: The median of apelin-13 was 495pg/mL . We found strong, negative correlation between the serum levels of apelin-13 and p<0.001). For the reassessed patients the median apelin level was significantly higher at follow-up (460 pg/mL, IQR 342-871 pg/mL) as compared with the baseline level (395 pg/mL, IQR 270-603 pg/mL), p=0.019, and maintained the negative correlation with p<0.001

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Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility

Cited by 561 publications

References 47 publications

Adipocyte-derived factors suppress heart contraction

Adipocyte-derived factors suppress heart contraction

The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice

Serum level of apelin-13 negatively correlated with NT-proBNP in heart failure patients

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