The direct relationship between obesity and cardiovascular diseases, such as, hypertension and coronary heart disease (CHD), is not understood at the molecular level. The receptors for leptin have been found in several tissues, including those in the cardiovascular system, suggesting that leptin may play a role in the regulation of cardiovascular functions. We have recently established that activation of the Jak/Stat signaling pathway is an essential component in maintaining the autocrine loop of the local tissue renin-angiotensin system (RAS) during cardiac hypertrophy. We further observed that the STAT proteins that are essential to maintain the autocrine loop of the heart tissue RAS are also the target of leptin. This observation along with the evidence on the presence of leptin receptors in the cardiovascular tissues prompted us to examine whether leptin is a potential regulator of the RAS and/or the cardiovascular function. Activation of the Jak/Stat pathway by leptin can induce the tissue RAS thereby linking obesity with hypertension, and perhaps with the mechanism underlying hypertrophic growth of the heart.
RECENT REFERENCES
1 Eduardo Mascareno, Manya Dhar and M.A.Q. Siddiqui. (1998) Signal transduction and activator of transcription (STAT) Protein-Dependent Activation of Angiotensinogen Promoter: A Cellular Signal for Hypertrophy in Cardiac Muscle. Proc. Natl. Acad. Sci. USA 95, 5590-5594.
2. Ghatpande S, Goswami S, Mascareno E, Siddiqui M.A.Q. Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy. Mol Cell Biochem (1999) 196:93-97.
3. Wagner M, Mascareno E, Siddiqui M.A.Q. Cardiac hypertrophy: signal transduction, transcriptional adaptation, and altered growth control. Ann. N Y Acad. Sci. (1999) 874:1-10
4. Manya Dhar, Eduardo Mascareno, and M. A. Q. Siddiqui. (1997) Two Distinct Factor-Binding Elements in Cardiac Myosin Light Chain 2 Gene Are Essential For Its Repression In Skeletal Muscle: Isolation Of cDNA Clone For Repressor Protein Nished. J. Biol. Chem. 27, 18490-18497.
5. E. Mascareno, and M.A.Q. Siddiqui The role of Jak/Stat signaling in heart tissue renin-angiotensin system. (2000) Mol. Cell. Biochem. (In Press).
EDUARDO MASCARENO, PhD
Research Assistant Professor
Department of Anatomy and Cell Biology, Box 5
Phone: 270-6701, Fax: 270-3732
E-mail: xjiang@downstate.edu
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