Abstract
Introduction: The APJ receptor and its ligand, apelin, comprise a homeostatic, cardio-regulatory pathway. Although cardiac apelin expression levels are altered in humans with cardiac failure, the cell type responsible for apelin expression and modulation in disease states remains unknown. Hypothesis: Apelin production is restricted to the endothelial compartment and is upregulated in states of cardiovascular stress. Methods: Transgenic apelin-LacZ reporter mice (SVJ background) were created by insertion of the nuclear localizing bacterial LacZ gene immediately downstream of the apelin promoter. Mice (n=12) were randomized to left anterior descending coronary artery (LAD) ligation, thoracic aortic constriction (TAC) or sham groups. Hearts were harvested 3 and 8 weeks post-TAC or LAD ligation, respectively. Localization of apelin expression was determined by Xgal staining. Endothelial phenotype of lacZ positive cells was confirmed by CD31 co-staining. Apelin expressing cells were quantified by histology. Apelin reporter results were confirmed by quantitating apelin expression in WT animals following LAD ligation (n=11) or sham (n=11) procedure by RT-PCR. Results: Extensive immunohistochemistry studies of heart tissue revealed lacZ reporter gene expression to be restricted to the coronary venous and capillary endothelium, with no expression by cardiomyocytes. Following both LAD ligation and TAC, the number of LacZ-apelin (+) endothelial cells significantly increased (p<0.002) in all chambers of the heart (Table ), with no evidence of apelin expression by other cell types. Evaluation of WT hearts by RT-PCR for the apelin gene confirmed the reporter gene findings with 1.3±0.3 fold increase (p<0.05) of apelin expression induced by LAD ligation compared to sham. Conclusions: Apelin is primary expressed by endothelial cells within the heart and is upregulated in response to myocardial stress. Apelin-LacZ Expressing Endothelial Cells are Increased Following Myocardial Injury
Published Version
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