REGULATION OF GENE EXPRESSION & FUNCTIONAL GENOMICS IN HEART DISEASE

Dr. Depre's research is focused on the regulation of gene expression and the functional genomics of heart disease, including myocardial ischemia and heart failure, both in animals and patients.  His laboratory is studying the genomic response of the heart in these different conditions to determine which cardioprotective mechanisms are developed in the stressed myocardium. This work has shown that unsuspected survival mechanisms are activated in the cardiac cells during ischemia, which may open new avenues to salvage dysfunctional myocardium. His laboratory is particularly interested in the cloning and characterization of novel genes, for which no function is known so far. Characterizing these new genes will improve the understanding as to how stressed myocardium can prevent cell death. Especially, these studies have illustrated that the heart can activate many genes participating to cell growth which were not described in myocardium before and which have been involved in the development and proliferation of cancer. The laboratory is currently working on the cardioprotective mechanisms of H11 kinase, an enzyme that participates in cardiac cell growth and cytoprotection against ischemia, but which is also involved in cancer development. Because of his training in both clinical cardiology and basic science, Dr. Depre is particularly interested in the bench-to-bedside approach of translational medicine and in the clinical applicability of laboratory research.

Recent Publications:

Depre C, Taegtmeyer H. Metabolic aspects of programmed cell survival and cell death in the heart. Cardiovasc Res (2000), 45: 538-548.  PubMed Citation

Vanoverschelde JLJ, Depre C, Gerber BL, Borgers M, Wijns W, Robert A, Dion R, Melin JA. Time-course of functional recovery after coronary bypass graft surgery in patients with chronic left ventricular dysfunction. Am J Cardiol (2000), 85: 1432-1439. PubMed Citation

Depre C, Ribicchini F, Wijns W. Morphological analysis of atherosclerotic plaque by directional coronary atherectomy. Semin Interv Cardiol (2000) 5: 175-184. PubMed Citation

Depre C, Tomlinson JE, Kudej RK, Thompson E, Gaussin V, Kim SJ, Vatner DE, Topper JN, Vatner SF. Gene program for cardiac cell survival induced by transient ischemia in conscious pigs. Proc Natl Acad Sci USA (2001), 98: 9336-9341. PubMed Citation

Young ME, Patil S, Ying J, Depre C, Ahuja HS, Shipley GL, Stepkowski SM, Davies PJA, Taegtmeyer H. Uncoupling protein 3 transcription in regulated by perozisome proliferator-activated receptor a in the adult rodent heart. FASEB J (2001), 15: 833-845. PubMed Citation

Ahuja HS, Liu S, Crombie DL, Boehm M, Leibowitz MD, Heyman RA, Depre C, Nagy L, Tontonoz P, Davies PJ. Differential effects of rexinoids and thiazolidinediones on metabloic gene expression in diabetic rodents. Mol Pharmacol (2001), 59: 765-773. PubMed Citation

Depre C , Gaussin V, Hase M, Zajac AQ, Wang L, Hittinger L, Ghaleh B, Yu X, Kudej RK, Wagner T, Sadoshima J, Vatner SF. H11 kinase is a novel mediator of cardiac hypertrophy in vivo. Circ Res (2002), 96: 1007-1014.

Depre C, Wang L, Tomlinson JE, Gaussin V, Abdellatif M, Topper JN, Vatner SF. Characterization of pDJA1, a cardiac-specific chaperone found by genomic profiling in the post-ischemic swine heart. Cardiovasc Res (2003), 58: 126-135.

Kim SJ, Depre C , Vatner SF. Novel mechanisms mediating stunned myocardium. Heart Fail Rev (2003), 8: 143-153.

Li J, Kim SJ, Takagi G, Yatani A, Zhang Q, Karoor V, Hong C, Yang G, Sadoshima J, Depre C , Vatner DE , West MJ , Vatner SF.  Neurally-mediated increase in calcineurin activity regulates cardiac contractile function in absence of hypertrophy. Cardiovasc Res (2003), 59: 649-65.

Gaussin V, Tomlinson JE, Depre C , Engelhardt S, Antos CL, Takagi G, Hein L, Topper JN, Liggett SB, Olson EN, Lohse MJ, Vatner SF, Vatner DE. Common genomic response in different mouse models of

b -adrenergic-induced cardiomyopathy. Circulation (2003), 108: 2926-2933.

Depre C , Kim SJ, John AS, Huang YH, Rimoldi OE, Pepper JR, Dreyfus GD, Gaussin V, Pennell DJ, Vatner DE , Camici PG, Vatner SF.  Program of cell survival underlying human and experimental hibernating myocardium. Circ Res (2004), 95:433-440.

Wang L, Zajac A, Hedhli N, Depre C.  Increased expression of H11 kinase stimulates glycogen synthesis in the heart. Mol Cell Biochem (2004), 265:71-78.

Hase M, Depre C , Vatner SF, Sadoshima J.  H11 has dose-dependent dual hypertrophic and proapoptotic functions in cardiac myocytes. Biochem J (2005), 388:475-483.

Depre C , Vatner SF: Mechanisms of cell survival in myocardial hibernation. Trends Cardiovas Med (2005) 15: 101-110.

Gaussin V, Morley GE, Cox L, Zwijsen A, Vance KM, Emile L, Tian Y, Liu J, Hong C, Myers D, Conway SJ, Depre C , Mishina Y, Behringer RR, Hanks MC, Schneider MD, Huylebroeck D, Fishman GI, Burch JBE, Vatner SF.  Alk3/Bmpr1a receptor is required for development of the atrioventricular canal into valves and annulus fibrosus. Circ Res (2005), 97:219-226.

Hedhli N, Pelat M, Depre C. Protein turnover in cardiac cell growth and survival. Cardiovasc Res (2005), 68:186-196.

Gaussin V, Depre C . Myostatin, the cardiac chalone of IGF-1. Cardiovasc Res (2005) 68: 347-349.

Depre C , Wang L, Sui X, Qiu H, Hong C, Hedhli N, Ginion A, Shah A, Pelat M, Bertrand L, Wagner T, Gaussin V, Vatner SF.  H11 Kinase prevents myocardial infarction by pre-emptive preconditioning of the heart. Circ Res (2006) 98: 280-288.

Depre C , Wang Q, Yan L, Hedhli N, Peter P, Chen L, Hong C, Hittinger L, Ghaleh B, Sadoshima J, Vatner DE, Vatner SF, Madura K. Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy . Circulation (2006), 114: 1821-1828.   

Rashed E, Depre C . Cardiac Cell Survival and Reversibility of Myocardial Ischemia. Arch Mal Coeur Vaiss (2006), 99: 1236-1243.

Danan IJ, Rashed ER, Depre C . Therapeutic potential of H11 Kinase for the ischemic heart. Cardiovasc Drug Revs (2007), 25: 14-29.

Qiu H, Yeh I, Tian B, Yan L, Resuello RG, Natividad FF, Peppas A, Shen YT, Vatner DE, Vatner SF, Depre C.  Sex-specific regulation of gene expression in the aging monkey aorta. Physiol Genomics (2007), 29: 169-180.

Kudej RK, Depre C . NO with no NOS in ischemic heart. Cardiovasc Res (2007) 74: 1-3.

Qiu H, Depre C , Vatner SF, Vatner DE. Sex differences in myocardial infarction and rupture. J Mol Cell Cardiol (2007), 43: 532-534.

Qiu H, Depre C , Yang G, Masurekar M, Yan L, Ge H, Resuello RG, Natividad FF, Rossi F, Peppas A, Shen YT, Vatner DE, Vatner SF. Mechanisms of gender-specific differences in aortic stiffness with aging in non-human primates. Circulation (2007), 116: 669-676.

Hedhli N, Wang L, Wang Q, Tian Y, Sui X, Madura K, Depre C . Proteasome activation during cardiac hypertrophy by the chaperone H11 Kinase/Hsp22. Cardiovasc Res (2007), in press.

Vitale JM, Qiu H, Depre C. Pre-emptive conditioning of the ischemic heart. Cardiovas Hem Agents Med Chem (2008), in press.