Apelin and pulmonary hypertension

• Published in: Pulmonary Circulation Vol. 1; no. 3; pp. 334 - 346
• Main Authors: Andersen, Charlotte U., Hilberg, Ole, Mellemkjœr, Søren, Nielsen-Kudsk, Jens E., Simonsen, U.
• Format: Journal Article Book Review
• Language: English
• Published: London, England University of Chicago Press 01-07-2011; SAGE Publications; Sage Publications Ltd. (UK); John Wiley & Sons, Inc; Medknow Publications & Media Pvt Ltd
• Subjects: Angiogenesis; Animal models; apelin; Apelin and the apelin receptor; aPJ; Blood pressure; Cell receptors; Development and progression; Endothelial cells; Heart; Heart ventricles; Hypoxia; Nitric oxide; Physiological aspects; Pulmonary arteries; Pulmonary artery; Pulmonary hypertension; Receptors; Review; Review Article; Smooth muscle; Smooth muscle myocytes; United States; aPJ; apelin; Apelin and the apelin receptor; pulmonary hypertension
• ISSN: 2045-8932; 2045-8940; 2045-8940
• DOI: 10.4103/2045-8932.87299

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin and the G-protein coupled apelin receptor (APLNR) are expressed in several tissues throughout the organism. Apelin is localized in vascular endothelial cells while the APLNR is localized in both endothelial and smooth muscle cells in vessels and in the heart. Apelin is regulated by hypoxia inducible factor -1α and bone morphogenetic protein receptor-2. Patients with PAH have lower levels of plasma-apelin, and decreased apelin expression in pulmonary endothelial cells. Apelin has therefore been proposed as a potential biomarker for PAH. Furthermore, apelin plays a role in angiogenesis and regulates endothelial and smooth muscle cell apoptosis and proliferation complementary and opposite to vascular endothelial growth factor. In the systemic circulation, apelin modulates endothelial nitric oxide synthase (eNOS) expression, induces eNOS-dependent vasodilatation, counteracts angiotensin-II mediated vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting potential new therapeutic target for PH.