Morris Karmazyn
Professor
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PH.D. McGil University |
The primary Research in my laboratory involves the understanding of the mechanisms of cardiac hypertrophy and heart failure and development of novel therapeutic strategies.
We are currently studying the cellular and molecular bases for heart failure with the ultimate aim of developing effective therapeutic strategies. Heart failure is an extremely complex syndrome underlined by a large number of molecular and changes. One of our major interests involves the sodium-hydrogen exchanger which appears to be a major contributor to myocardial remodelling including hypertrophy which contributes to the heart failure process. We have already demonstrated that blocking the exchanger reduces hypertrophy and heart failure in experimental animals. We use a wide variety of methodologies ranging from molecular to intact organisms. For example, using cultured rat ventricular myocytes we are studying the molecular bases for induction of hypertrophy and the role of key genes in this process. We are also utilizing animal models such as the rat myocardial infarction model to assess the effects of novel approaches on the postinfarction hypertrophic process. As part of the Heart and Stroke Foundation Program in Heart Failure (www.heartfailuregroup.uwo.ca), our laboratory offers the opportunity to investigate heart failure using multifaceted collaborative approaches with other members of group with the ultimate goal to develop novel strategies for treating heart failure.
There are 4 major research areas which we are currently pursuing in relation to cardiac hypertrophy and heart failure: 1) Na-H Exchange (Supported by the Canadian Institutes of Health Research); 2) Leptin (Supported by the Canadian Institutes of Health Research); 3) Adenosine (Supported by the Canadian Institutes of Health Research); 4) Endothelin-nitric oxide interaction (Supported by the Heart and Stroke Foundation of Ontario)
Zeidan A, Javadov S, Karmazyn M. Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating leptin-induced hypertrophy in rat neonatal ventricular myocytes. Cardiovasc Res. 2006 Jun 29; [Epub ahead of print] Rajapurohitam V, Javadov S, Purdham DM, Kirshenbaum LA, Karmazyn M. An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1. J Mol Cell Cardiol. 2006 Aug;41(2):265-74. Epub 2006 Jun 23. Javadov S, Purdham DM, Zeidan A, Karmazyn M. NHE-1 inhibition improves cardiac mitochondrial function through regulation of mitochondrial biogenesis during postinfarction remodeling. Am J Physiol Heart Circ Physiol. 2006 May 5; [Epub ahead of print] Zou MX, Roy AA, Zhao Q, Kirshenbaum LA, Karmazyn M, Chidiac P. RGS2 is upregulated by and attenuates the hypertrophic effect of alpha(1)-adrenergic activation in cultured ventricular myocytes. Cell Signal. 2006 Oct;18(10):1655-63. Epub 2006 Mar 6. Javadov S, Baetz D, Rajapurohitam V, Zeidan A, Kirshenbaum LA, Karmazyn M. Antihypertrophic effect of Na+/H+ exchanger isoform 1 inhibition is mediated by reduced mitogen-activated protein kinase activation secondary to improved mitochondrial integrity and decreased generation of mitochondrial-derived reactive oxygen species. J Pharmacol Exp Ther. 2006 Jun;317(3):1036-43. Epub 2006 Mar 2.
