Abstract 463: Hypoxia is a Primary Stimulus for Up-Regulation of the Apelin-APJ Cardio-Regulatory Pathway
Introduction: The APJ receptor and its ligand, apelin, comprise a homeostatic, cardioregulatory pathway. Apelin is an inotrope and reduces afterload by decreasing vasomotor tone. In humans, heart failure causes upregulation of apelin and APJ, but the stimuli eliciting this response remain unknown.
Hypothesis: Hypoxia induces upregulation of the apelin-APJ pathway.
Methods: Triplicate sets of human coronary artery endothelial cells and murine skeletal myoblasts were kept hypoxic (1% O2) or normoxic for 24h, followed by RNA extraction. Adult female WT SVJ 129 mice (n=20) and transgenic apelin-LacZ reporter mice (n=4) were randomized to systemic hypoxia (10% FiO2) or ambient PO2 for 1 week. Hearts, lungs, and quadriceps were harvested. RNA from cultured cells and WT animal tissues were analyzed for apelin and APJ expression by TaqMan RT-PCR. Localization of apelin expression was determined by β-galactosidase staining of tissues from apelin-LacZ reporter mice.
Results: Hypoxia induced 2.4±0.4* and 4.5±0.5* fold increases in apelin expression by endothelial cells and myoblasts, respectively. Both apelin and APJ expression were significantly* increased in heart and lungs following systemic hypoxia, with a near 8-fold increase in cardiac apelin (Fig 1B⇓). LacZ staining revealed endothelial-specific expression of apelin in the heart, lung, and quadriceps in both normoxic and hypoxic animals. *p<0.001.
Conclusions: Hypoxia is a potent stimulator of apelin and APJ expression, suggesting a primary role for hypoxia-induced upregulation of this pathway in pathophysiological states such as ischemic heart failure.