Circulating and cardiac levels of apelin, novel ligand of the orphan receptor APJ, in patients with heart failure

Földes, Gábor; Horkay, Ferenc; Szokodi, István; Vuolteenaho, Olli; Ilves, Mika; Lindstedt, Ken A.; Sármán, Balázs; deChâtel, Rudolf; Ruskoaho, Heikki; Tóth, Miklós

doi:10.1016/s0895-7061(03)00117-1

Cited by 37 publications

(56 citation statements)

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“…Whereas in the adult rat lung, apelin presence is strongest in the alveolar epithelium, less intense in the bronchial epithelium and nearly absent in the vasculature. Interestingly there is apelin immunoreactivity in the content of the pulmonary blood vessels which is not associated with blood cells, which may possibly be in accordance with previous reports that detected plasma levels of apelin in humans and consequently showed that apelin is a circulating peptide [6,13,16]. Few studies report apelin localization in pulmonary tissue by immunohistochemistry, showing intense staining in the respiratory epithelium and smooth muscle in normal adult human tissues [10], and also presence in bronchial and alveolar epithelial cells in neonatal rat lung [47].…”

Section: Discussionsupporting

confidence: 91%

The apelinergic system in the developing lung: Expression and signaling

et al. 2011

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a b s t r a c tApelin and its receptor APJ constitute a signaling pathway best recognized as an important regulator of cardiovascular homeostasis. This multifunctional peptidergic system is currently being described to be involved in embryonic events which extend into vascular, ocular and heart development. Additionally, it is highly expressed in pulmonary tissue. Therefore, the aim of this study was to investigate the role of apelinergic system during fetal lung development. Immunohistochemistry and Western blot analysis were used to characterize apelin and APJ expression levels and cellular localization in normal fetal rat lungs, at five different gestational ages as well as in the adult. Fetal rat lung explants were cultured in vitro with increasing doses of apelin. Treated lung explants were morphometrically analyzed and assessed for MAPK signaling modifications. Both components of the apelinergic system are constitutively expressed in the developing lung, with APJ exhibiting monomeric, dimeric and oligomeric forms in the pulmonary tissue. Pulmonary epithelium also displayed constitutive nuclear localization of the receptor. Fetal apelin expression is higher than adult expression. Apelin supplementation inhibitory effect on branching morphogenesis was associated with a dose dependent decrease in p38 and JNK phosphorylation. The results presented provide the first evidence of the presence of an apelinergic system operating in the developing lung. Our findings also suggest that apelin inhibits fetal lung growth by suppressing p38 and JNK signaling pathways.

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Section: Discussionsupporting

confidence: 91%

The apelinergic system in the developing lung: Expression and signaling

et al. 2011

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“…To our knowledge, there are no differences reported so far between genders, but already published studies either have a limited number of female subjects [15,[37][38][39], or the research focused mainly on male subjects [13,40]. The fact that there were no differences between genders other than apelin-13 level, NYHA class and LV mass and that apelin-13 was weakly correlated with LV mass when all subjects were analyzed (patients and controls) (Spearman's rho 0.28, p=0.023) give grounds for further research.…”

Section: Discussionmentioning

confidence: 95%

“…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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“…During heart failure, plasma apelin levels rise in the early stages of disease and stabilise or lower as the condition develops (Chen et al 2003, Chong et al 2006, Miettinen et al 2007). However, APJ mRNA is decreased in the weakened and enlarged heart of humans with idiopathic dilated cardiomyopathy (Foldes et al 2003). Apelin may have a cardioprotective role in hypoxia and ischaemia, where the cardiac levels of apelin and APJ respectively are increased (Atluri et al 2007, Ronkainen et al 2007, Zeng et al 2009).…”

Section: Cardiovascular Roles Of Apelin/apjmentioning

confidence: 99%

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

O’Carroll

Lolait

Harris

et al. 2013

Journal of Endocrinology

288

216

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The apelin receptor (APJ; gene symbol APLNR) is a member of the G protein-coupled receptor gene family. Neural gene expression patterns of APJ, and its cognate ligand apelin, in the brain implicate the apelinergic system in the regulation of a number of physiological processes. APJ and apelin are highly expressed in the hypothalamo-neurohypophysial system, which regulates fluid homeostasis, in the hypothalamic-pituitary-adrenal axis, which controls the neuroendocrine response to stress, and in the forebrain and lower brainstem regions, which are involved in cardiovascular function. Recently, apelin, synthesised and secreted by adipocytes, has been described as a beneficial adipokine related to obesity, and there is growing awareness of a potential role for apelin and APJ in glucose and energy metabolism. In this review we provide a comprehensive overview of the structure, expression pattern and regulation of apelin and its receptor, as well as the main second messengers and signalling proteins activated by apelin. We also highlight the physiological and pathological roles that support this system as a novel therapeutic target for pharmacological intervention in treating conditions related to altered water balance, stress-induced disorders such as anxiety and depression, and cardiovascular and metabolic disorders.

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Circulating and cardiac levels of apelin, novel ligand of the orphan receptor APJ, in patients with heart failure

Cited by 37 publications

References 0 publications

The apelinergic system in the developing lung: Expression and signaling

The apelinergic system in the developing lung: Expression and signaling

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

The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis

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