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Signal Transduction and Cardiac Hypertrophy pp 349–356Cite as

JAK/Stat Signaling in Cardiac Diseases

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

Summary

The molecular mechanisms that initiate and propagate myocardial diseases are known to involve participation of distinct signaling pathways. The onset of myocardial hypertrophy and ischemia followed by reperfusion, hypoxia/reoxygenation and oxygen radicals is accompanied by an upregulated level of the heart tissue-localized renin-angiotensin system (RAS). The major signaling events attributed to the RAS are the G-protein receptor signaling and those that are associated with the redox regulated system. The cross-talk likely to occur between these pathways may reach a putative focal point needed to program the execution of the disease related transcriptional events. In this context, the JAK2/Stat proteins play a pivotal role. Our studies support the notion that signals induced by diverse stimuli are somehow linked to the activated Janus Kinase-2 (JAK2) which appears to be the determining factor in triggering the execution of the disease related genetic program in cardiomyocytes. If this signaling pathway in cardiomyocyte plays a role in initiation and progression of cardiac diseases, specific inhibitors of the components of the pathway might be important as therapeutic agents. Selective inhibition of JAK2 by AG490 caused a reduction of cardiac hypertrophy, ischemic injury and cell death and a simultaneous increase in cardiac function. These observations thus provide new conceptual paradigms in heart disease research making it possible to develop novel cardioprotective agents mechanistically based on modulation in signaling events.

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Authors and Affiliations

  1. Center for Cardiovascular and Muscle Research, Department of Anatomy and Cell Biology, Downstate Medical Center, State University of New York, 450 Clarkson Avenue, Brooklyn, New York, 11203, USA

    M. A. Q. Siddiqui & Eduardo Mascareno

Authors
  1. M. A. Q. Siddiqui
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  2. Eduardo Mascareno
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Corresponding author

Correspondence to M. A. Q. Siddiqui .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

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Siddiqui, M.A.Q., Mascareno, E. (2003). JAK/Stat Signaling in Cardiac Diseases. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_25

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  • DOI: https://doi.org/10.1007/978-1-4615-0347-7_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5032-3

  • Online ISBN: 978-1-4615-0347-7

  • eBook Packages: Springer Book Archive

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