HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 294/1/H88    most recent 00935.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Sheikh, A. Y. Articles by Quertermous, T. Search for Related Content PubMed PubMed Citation Articles by Sheikh, A. Y. Articles by Quertermous, T.

In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure

Departments of ¹Cardiothoracic Surgery, ²Medicine, and ³Pathology, Stanford University School of Medicine, Stanford, California

Submitted 13 August 2007 ; accepted in final form 27 September 2007

Signaling by the peptide ligand apelin and its cognate G protein-coupled receptor APJ has a potent inotropic effect on cardiac contractility and modulates systemic vascular resistance through nitric oxide-dependent signaling. In addition, there is evidence for counterregulation of the angiotensin and vasopressin pathways. Regulatory stimuli of the apelin-APJ pathway are of obvious importance but remain to be elucidated. To better understand the physiological response of apelin-APJ to disease states such as heart failure and to elucidate the mechanism by which such a response might occur, we have used the murine model of left anterior descending coronary artery ligation-induced ischemic cardiac failure. To identify the key cells responsible for modulation and production of apelin in vivo, we have created a novel apelin-lacZ reporter mouse. Data from these studies demonstrate that apelin and APJ are upregulated in the heart and skeletal muscle following myocardial injury and suggest that apelin expression remains restricted to the endothelium. In cardiac failure, endothelial apelin expression correlates with other hypoxia-responsive genes, and in healthy animals both apelin and APJ are markedly upregulated in various tissues following systemic hypoxic exposure. Experiments with cultured endothelial cells in vitro show apelin mRNA and protein levels to be increased by hypoxia, through a hypoxia-inducible factor-mediated pathway. These studies suggest that apelin-expressing endothelial cells respond to conditions associated with heart failure, possibly including local tissue hypoxia, and modulate apelin-APJ expression to regulate cardiovascular homeostasis. The apelin-APJ pathway may thus provide a mechanism for systemic endothelial monitoring of tissue perfusion and adaptive regulation of cardiovascular function.

congestive heart failure; endothelium; gene expression

This article has been cited by other articles:

				D. N. Charo, M. Ho, G. Fajardo, M. Kawana, R. K. Kundu, A. Y. Sheikh, T. P. Finsterbach, N. J. Leeper, K. V. Ernst, M. M. Chen, et al. Endogenous regulation of cardiovascular function by apelin-APJ Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1904 - H1913. [Abstract] [Full Text] [PDF]

				R. A.P. Weir, K. S. Chong, J. R. Dalzell, C. J. Petrie, C. A. Murphy, T. Steedman, P. B. Mark, T. A. McDonagh, H. J. Dargie, and J. J.V. McMurray Plasma apelin concentration is depressed following acute myocardial infarction in man Eur J Heart Fail, June 1, 2009; 11(6): 551 - 558. [Abstract] [Full Text] [PDF]

				S. Han, G. Wang, X. Qi, H. M. Lee, E. W. Englander, and G. H. Greeley Jr. A possible role for hypoxia-induced apelin expression in enteric cell proliferation Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1832 - R1839. [Abstract] [Full Text] [PDF]