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We tested the hypothesis that myocardial ischemia-reperfusion (I/R)-induced apoptosis is attenuated in transgenic mice overexpressing cardiac [A.sub.1] adenosine receptors. Isolated hearts from transgenic (TG, n = 19) and wild-type (WT, n = 22) mice underwent 30 min of ischemia and 2 h of reperfusion, with evaluation of apoptosis, caspase 3 activity, function, and necrosis. I/R-induced apoptosis was attenuated in TG hearts. TG hearts had less If R-induced apoptotic nuclei (0.88 [+ or -] 0.10% vs. 4.22 [+ or -] 0.24% terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in WT, P < 0.05), less DNA fragmentation (3.30 [+ or -] 0.38-fold vs. 4.90 [+ or -] 0.39-fold over control in WT, P < 0.05), and less If R-induced caspase 3 activity (145 [+ or -] 25% over nonischemic control vs. 234 [+ or -] 31% in WT, P < 0.05). TG hearts also had improved recovery of function and less necrosis than WT hearts. In TG hearts pretreated with LY-294002 (3 [micro]M) to evaluate the role of phosphosinositol-3-kinase in acute signaling, there was no change in the functional protection or apoptotic response to UR. These data suggest that cardio-protection with transgenic overexpression of [A.sub.1] adenosine receptors involves attenuation of UR-induced apoptosis that does not involve acute signaling through phosphoinositol-3-kinase. cardioprotection; ischemia-reperfusion injury; transgenic mice; phosphoinositol-3-kinase

Cardiac gene expression profile and lipid accumulation in response to starvation. Am J Physiol Endocrinol Metab 46: E94-E102, 2002. First published March 5, 2002; 10.1152/ajpendo.00017.2002.--Starvation induces many biochemical and histological changes in the heart; however, the molecular events underlying these changes have not been fully elucidated. To explore the molecular response of the heart to starvation, microarray analysis was performed together with biochemical and histological investigations. Serum free fatty acids increased twofold in both 16- and 48-h-fasted mice, and cardiac triglyceride content increased threefold and sixfold in 16- and 48-h-fasted mice, respectively. Electron microscopy showed numerous lipid droplets in hearts of 48-h-fasted mice, whereas fewer numbers of droplets were seen in hearts from 16-h-fasted mice. Expression of 11,000 cardiac genes was screened by microarrays. More than 50 and 150 known genes were detected by differential expression analysis after 16- and 48-h-fasts, respectively. Genes for fatty acid oxidation and gluconeogenesis were increased, and genes for glycolysis were decreased. Many other genes for metabolism, signaling/cell cycle, cytoskeleton, and tissue antigens were affected by fasting. These data provide a broad perspective of the molecular events occurring physiologically in the heart in response to starvation. microarray analysis; differential expression; lipid droplet