Eduardo Mascareno, PhD

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.

• Mascareno E, Gupta R, Martello LA, Dhar-Mascareno M, Salciccioli L, Beckles D, Walsh MG, Machado FS, Tanowitz HB, Haseeb MA. (2017) Rapidly progressive course of Trypanosome cruzi infection in mice heterozygous for hexamethylene bis-acetamide inducible 1 (Hexim1) gene. Microbes Infect. S1286-4579(17) 30145-4 PMID 28951318.
• Dhar-Mascareno M, Rozenberg I, Iqbal J, Hussain MM, Beckles D, Mascareno E. (2017) Hexim1 heterozygosity stabilizes atherosclerotic plaque and decreases steatosis in ApoE null mice fed atherogenic diet. Int J Biochem Cell Biol. 83: 56-64. PMID 28013147
• Dhar-Mascareno M, Ramirez SN, Rozenberg I, Rouille Y, Kral JG, Mascareno EJ. (2016) Hexim1, a novel regulator of Leptin function, modulates obesity and glucose disposal. Mol Endocrinol 30(3): 314-24. PMID: 26859361
• Martello LA, Wadgaonkar R, Gupta R, Machado FS, Walsh MG, MascarenoE, Tanowitz HB, Haseeb MA. (2013) Characterization of Trypanosoma cruzi infectivity, proliferation, and cytokine patterns in gut and pancreatic epithelial cells maintained in vitro. Parasitol Res. 2013 112 (12) 4177-83.
• Mascareno E, Galatioto J, Rozenberg I, Salciccioli L, Kamran H, Lazar JM, Liu F, Pedrazzini T, Siddiqui MA. (2012) Cardiac lineage protein-1 (CLP-1) regulates cardiac remodeling via transcriptional modulation of diverse hypertrophic and fibrotic responses and angiotensin II-transforming growth factor β (TGF-β1) signaling axis. J Biol Chem. Apr 13; ; 287(16):13084-93.
• Mascareno EJ, Belashov I, Siddiqui MA, Liu F, Dhar-MascarenoM.(2012) Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer.Prostate. Jun 15;72(9):1035-44.
• Galatioto J, MascarenoE, Siddiqui MAQ (2010) CLP-1 associates with MyoD and HDAC to restore skeletal muscle regeneration. J Cell Sci. 2010, 123: 3789-3795.
• Manukyan I,Galatioto J, Mascareno E, Bhaduri S, Siddiqui MAQ (2010) Cross-talk between Calcineurin/NFAT and Jak/STAT signaling induces cardioprotective B-crystallin gene expression in response to hypertrophic stimuli J Cell Mol Med 14(6B):1707-16.
• Gurusamy N, Lekli I, Ahsan MK, Ray D, Mukherjee S, Mascareno E, Siddiqui MAQ, and Das DK. (2010) Downregulation of Cardiac Lineage Protein-1 confers cardioprotection through the upregulation of Redox effectors FEBS Letters 584:187- 193.
• Mascareno E, Beckles D, Dhar-Mascareno M, Siddiqui MAQ (2009) Enhanced hypertrophy in ob/ob mice due to an impairment in expression of atrial natriuretic peptide. Vasc Pharmacol 51: 198-204.
• Epinoza-Derout J, Wagner M, Salciccioli L, Lazar JM, Bhaduri S, Mascareno E, Chaqouir B, Siddiqui MA (2009) Positive transcription elongation factor B activity in compensatory myocardial hypertrophy is regulated by cardiac lineage protein-1. Circ Res 104: 1347-1354.
• Dhar-Mascareno M, Mascareno E, Golde D (2009) Early signaling by VEGF and PIGF in human bone marrow derived endothelial cells in mediated by superoxide. J Vasc Res 46: 601-608.
• Mascareno E, Manukyan I, Das DK, Siddiqui MAQ (2009) Downregulation of cardiac lineage protein (CLP-1) expression in CLP-1 +/- mice affords cardioprotection against ischemic stress. J Cell Mol Med 13(8B):2744-53.
• Mathew S, Galatioto J, Mascareno E, Siddiqui MAQ (2009) Repression of the cardiac Myosin light chain-2 gene in skeletal muscle requires site specific association of antithetic regulator, Nished, and HDACs. J Cell Mol Med 13(8B):1952-61.

List of Publications (Pub Med)

Reviews/Chapters

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