The primary objective of the Animal Hypoxia (Core C) is to provide standardized chronic exposures of sustained and intermittent hypoxia and/or hypercapnia to flies and mice used by all of the Projects, and to characterize the essential respiratory and cardiovascular phenotypes in the different species, genotypes, and exposures studied by the individual Projects. Standardizing exposure is vital for integrating the findings between the different Projects and optimizing data sharing. Centralizing this also insures quality control and dissemination of any results from individual Projects suggesting that the exposure protocols should be adjusted. Importantly, this centralization also conserves animals and resources to maximize the budget and animal sacrifice. Behavioral measurements are not included in this revised proposal but the larger Biospherix chambers, which house multiple animals and cages will be used for all chronic exposures to insure identical social interactions and conditioning. Phenotyping mice in the core also minimizes the cost and maximizes the information individual animal models in terms of the basic metabolic, respiratory and cardiovascular physiology that is necessary for all of the individual Projects. Given the challenges of maintaining disease free-breeding colonies for multiple lines of transgenic mice, it is most efficient and cost effective to make non-invasive and non-terminal descriptive measurements within a physiology core facility before distributing chronically exposed animals to individual laboratories for the actual experiments. Physiological data will be uploaded to a database developed with Systems Biology Core B for all the investigators to use so the projects can focus on the biology. Training in the physiological techniques used to phenotype the animals will also be provided by Core C to predoctoral students and postdoctoral fellows working in the individual Projects.

Public Health Relevance

Chronic hypoxemia is a large health problem with many cardiovascular and lung diseases. For example, sustained (continuous) hypoxemia occurs with emphysema and intermittent hypoxemia occurs with sleepdisordered breathing. The health impact of intermittent hypoxia is especially large considering sleepdisordered breathing occurs in at least 2-4% of adults. Understanding the genetic and physiological basis of tolerance and susceptibility tochronic hypoxia is necessary to improve treatment of these diseases.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of California San Diego
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Yamamura, Hisao; Yamamura, Aya; Ko, Eun A et al. (2014) Activation of Notch signaling by short-term treatment with Jagged-1 enhances store-operated Ca(2+) entry in human pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol 306:C871-8
Smith, Kimberly A; Yuan, Jason X-J (2014) Hypoxia-inducible factor-1? in pulmonary arterial smooth muscle cells and hypoxia-induced pulmonary hypertension. Am J Respir Crit Care Med 189:245-6
Lim, Hui-Ying; Wang, Weidong; Chen, Jianming et al. (2014) ROS regulate cardiac function via a distinct paracrine mechanism. Cell Rep 7:35-44
Nishimura, Mayuko; Kumsta, Caroline; Kaushik, Gaurav et al. (2014) A dual role for integrin-linked kinase and ?1-integrin in modulating cardiac aging. Aging Cell 13:431-40
Kang, Yunyi; Tiziani, Stefano; Park, Goonho et al. (2014) Cellular protection using Flt3 and PI3K? inhibitors demonstrates multiple mechanisms of oxidative glutamate toxicity. Nat Commun 5:3672
Song, Shanshan; Yamamura, Aya; Yamamura, Hisao et al. (2014) Flow shear stress enhances intracellular Ca2+ signaling in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension. Am J Physiol Cell Physiol 307:C373-83
Lathen, Christopher; Zhang, Yu; Chow, Jennifer et al. (2014) ERG-APLNR axis controls pulmonary venule endothelial proliferation in pulmonary veno-occlusive disease. Circulation 130:1179-91
Pfeiffer, E R; Wright, A T; Edwards, A G et al. (2014) Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing. J Mol Cell Cardiol 76:265-74
Ronen, Roy; Zhou, Dan; Bafna, Vineet et al. (2014) The genetic basis of chronic mountain sickness. Physiology (Bethesda) 29:403-12
Gan, Zhuohui; Wang, Jianwu; Salomonis, Nathan et al. (2014) MAAMD: a workflow to standardize meta-analyses and comparison of affymetrix microarray data. BMC Bioinformatics 15:69

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