Department of Cell Biology Faculty

Leptin: A Regulator of the Cardiovascular System

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.

PUBLICATIONS

1. Espinoza-Derout J., Wagner M., Shahmiri K., Mascareno E., Chaqour B., Siddiqui MAQ. Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy. Cardiovasc Res. 2007, 75(1):129-38.

2. Beckles DL, Mascareno E., Siddiqui MAQ. Inhibition of Jak2 phosphorylation attenuates pressure overload cardiac hypertrophy. Vascul. Pharmacol. 2006 May 23; [Epub ahead of print] (Equal contribution).

3. Mascareno E., Beckles DL, Siddiqui MAQ. Janus kinase-2 signaling mediates apoptosis in rat cardiomyocytes. Vascul. Pharmacol. 2005 43(5):327-35.

4. Guaiquil V.H., Golde D.W., Beckles D.L., Mascareno E.J., Siddiqui MAQ. Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts. Free Radic. Biol. Med. 2004 37(9):1419-29.

5. Mathew S., Mascareno E., Siddiqui MAQ. A ternary complex of transcription factors, Nished and NFATc4, and co-activator p300 bound to an intronic sequence, intronic regulatory element, is pivotal for the up-regulation of myosin light chain-2v gene in cardiac hypertrophy. J Biol Chem. 2004 279(39):41018-27. (Equal contribution)

6. Guo Y., Mascareno E., Siddiqui MAQ. Distinct components of Janus kinase/signal transducer and activator of transcription signaling pathway mediate the regulation of systemic and tissue localized renin-angiotensin system. Mol Endocrinol. 2004 18(4):1033-41.

7. El-Adawi H., Deng L., Tramontano A., Smith S., Mascareno E., Ganguly K., Castillo R, El-Sherif N. The functional role of the JAK-STAT pathway in post-infarction remodeling. Cardiovasc. Res. 2003 57(1):129-38.

8. Mascareno E., El-Shafei M., Maulik N., Sato M., Guo Y., Das D.K., Siddiqui MAQ. JAK/STAT signaling is associated with cardiac dysfunction during ischemia and reperfusion. Circulation. 2001 104(3):325-9.

List of Publications (Pub Med)

 

REVIEWS/CHAPTERS

1. Siddiqui MAQ and Mascareno, E. Jak/Stat signaling in cardiac diseases. Book entitled Signal Transduction and Cardiac Hypertrophy. Edited Kluwer Academic Publishers (2002).

2. Siddiqui, MAQ, Wagner M, Mascareno E and Shafiq S. Signal transduction in Myofibrillogenesis, Cell Growth and Hypertrophy. Cardiovascular Molecular Morphogenesis. (2001) Chapter 9: 143-152.

3. Mascareno E., Siddiqui MAQ. The role of Jak/STAT signaling in heart tissue renin-angiotensin system. Mol Cell Biochem. 2000 212(1-2):171-5.