Rakeshwar Guleria, PhD
Research Assistant Professor
Education and Post-Graduate Training
MSc, Microbiology, Dr. Rammanohar Lohia University,India, 1997
PhD, Biochemistry, King George's Medical University and University of Lucknow,India, 2002
Post-doctoral Research Associate, Texas A&M University College of Medicine, Temple, Texas, 2004-2009
Instructor, Department of Medicine, Texas A&M Health Sciences Center College of Medicine, Temple, Texas-2009-2011.
Role of renin angiotensin system in diabetes induced cardiac remodeling with special reference to retinoid receptor mediated signaling
Vitamin A (retinol) and its natural and synthetic derivatives (retinoid) participate in a wide range of biological processes, including vision, neoplasia, embryonic development, normal reproductive function, regulation of epithelial and hematopoietic cellular differentiation, and cardiovascular development. Retinoic acid (RA), the active metabolite of vitamin A, is the main signaling retinoid in the body. RA functions by binding to nuclear receptor proteins. Two families of retinoid receptors exist: the RARs family comprises three distinct genes (RARα, β and γ), whose encoded proteins bind both all-transRA (atRA) and 9-cis RA, and the RXRs family, which also contains three members (RXRα, β and γ) that preferentially bind 9-cis RA. These ligand-activated retinoid receptors act as transcription factors which bind to RA response elements in the promoters/enhancers of numerous target genes, leading to transcriptional stimulation or repression.
Deficiency of vitamin A or embryonic deletion of selected retinoid receptors has been linked to a variety of defects in cardiovascular development. In the post-development period, retinoid are required for the proper functioning of a number of organs (skin, lung, liver, neuronal and immune systems) and have important regulatory activity in the cardiovascular system. Numerous studies have focused on characterization of the intracellular signal transduction molecules that promote cardiac hypertrophy; but, little work has focused on signaling pathways that might negatively regulate hypertrophy. Retinoid have been shown to have significant anti-hypertrophic effects in neonatal cardiomyocytes. Our study also demonstrated that RA has suppression effects on cyclic stretch-iniduced cardiac hypertrophy. However, the signaling mechanism of RA-induced inhibitory effects on the hypertrophic process are not clear. Currently, we are investigating the molecular mechanism of retinoic acid mediated inhibition of cardiac growth and its regulation of the renin-angiotensin system in the heart.
Diabetes mellitus is a key risk factor for cardiovascular diseases and heart failure. Enhanced expression and activation of renin-angiotensin system components has been implicated in the development of diabetes induced cardiac remodeling. We observed that the high glucose-induced synthesis of Ang II was suppressed by retinoic acid. This observation generated lot of enthusiasm and currently we are also investigating the role of retinoic acid signaling in diabetes-induced development of cardiac remodeling by using in vitro and in vivo systems.
Council of Scientific and Industrial Research Fellowship (CSIR), India - 1997
Fellowship from International Clinical Epidemiology Network (INCLEN)/WHO/Johns Hopkins School of Public Health USA - 2000-2001
Fellowship from Department of Science and Technology (DST), India - 2001-2002
Young Investigator Award, Texas A&M Health Science Center, Texas, 2006
Best Manuscript Award, Texas A&M Health Science Center, Texas, 2007
- Guleria RS, Pan J, Dipette D, Singh US. Hyperglycemia inhibits retinoic acid-induced activation of Rac1, prevents differentiation of cortical neurons, and causes oxidative stress in a rat model of diabetic pregnancy. Diabetes. 2006 Dec;55(12):3326-34. PMID: 17130476
- Lal H, Verma SK, Guleria RS, Smith M, Foster DM, Dostal DE. Stretch-Induced MAP kinase activation in cardiac myocytes: differential regulation through beta1-integrin and focal adhesion kinase. J Mol Cell Cardiol. 2007 Aug;43(2):137-47. PMID: 17583725; PMCID: PMC2039913
- Guleria RS, Choudhary R, Tanaka T, Baker KM, Pan J. Retinoic acid receptor-mediated signaling protects cardiomyocytes from hyperglycemia induced apoptosis: role of the renin-angiotensin system. J Cell Physiol. 2011 May;226(5):1292-307. doi: 10.1002/jc.22457. PMID: 20945395; PMCID: PMC3043168
- Verma SK, Lal H, Golden HB, Gerilechaogetu F, Smith M, Guleria RS, Foster DM, Lu G, Dostal DE. Rac1 and RhoA differentially regulate angiotensinogen gene expression in stretched cardiac fibroblasts. Cardiovasc Res. 2011 Apr 1;90(1):88-96. doi: 10.1093/cvr/cvq385. PMID: 21131638; PMCID: PMC3058736
- Guleria RS, Singh AB, Nizamutdinova IT, Souslova T, Mohammad AA, Kendall JA Jr, Baker KM, Pan J. Activation of retinoid receptor-mediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats. J Mol Cell Cardiol. 2013 Apr;57:106-18. doi: 10.1016/j.yjmcc.2013.01.017. PMID: 23395853; PMCID: PMC3594065