MECHANISMS OF CARDIOVASCULAR CONTROL

Dr. Vatner's research aims are directed at expanding the knowledge of mechanisms of cardiovascular control in normal and disease states; these discoveries have led to innovative new approaches to the treatment of heart and blood vessel diseases. He has made important contributions to the understanding of cardiovascular mechanisms at the molecular level, including those regulating adrenergic neural control, exercise and inotropic state. As an integrative physiologist, he has been a pioneer in delineating how normal physiologic controls that go astray can contribute to the pathogenes in myocardial ischemia, heart failure and reperfusion injury.

In 1975, Dr. Vatner and his colleagues published studies describing a new concept in the control of ischemic heart, myocardial stunning. This seminal work opened the way to the now-accepted concepts of myocardial hibernation, reperfusion injury, cardiac protection and pre-conditioning. When coronary vasospasm was receiving renewed attention, his research provided insights into coronary artery diameter control. More recently, Dr. Vatner has used transgenic animals to identify altered cardiovascular control mechanisms and receptor coupling in the disease process of hear failure. His findings are documented in more than 350 peer-reviewed scientific publications.

In addition to his research, Dr. Vatner has also made significant contributions to the academic and scientific communities and the area of public service. He has trained more than 90 postdoctoral research fellows (since 1972), including more than 20 who now hold full professorships. From 1991 to 1999, he was editor-in-chief of the American Heart Association journal Circulation Research.

Representative Publications:  

Yang G, Meguro T, Hong C, Asai K, Takagi G, Karoor VL, Sadoshima J, Vatner DE, Bishop SP, Vatner SF. Cyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis. J Mol Cell Cardiol. 2001 33(8):1505-1514.  PubMed Citation

Hardt SE, Geng YJ, Montagne O, Asai K, Hong C, Yang GP, Bishop SP, Kim SJ, Vatner DE, Seidman CE, Seidman JG, Homcy CJ, Vatner SF. Accelerated cardiomyopathy in mice with overexpression of cardiac G(s)alpha and a missense mutation in the alpha-myosin heavy chain. Circulation. 2002 105(5):614-620. PubMed Citation

Kim YK, Kim SJ, Kramer CM, Yatani A, Takagi G, Mankad S, Szigeti GP, Singh D, Bishop SP, Shannon RP, Vatner DE, Vatner SF. Altered excitation-contraction coupling in myocytes from remodeled myocardium after chronic myocardial infarction. J Mol Cell Cardiol. 2002 34(1):63-73. PubMed Citation

Lewandowski ED, Kudej RK, White LT, O'Donnell JM, Vatner SF. Mitochondrial preference for short chain fatty acid oxidation during coronary artery constriction. Circulation. 2002 105(3):367-372. PubMed Citation

Kim SJ, Kim YK, Takagi G, Huang CH, Geng YJ, Vatner SF. Enhanced iNOS function in myocytes one day after brief ischemic episode. Am J Physiol Heart Circ Physiol. 2002 282(2):H423-428. PubMed Citation

Yamamoto S, Yang G, Zablocki D, Liu J, Hong C, Kim SJ, Soler S, Odashima M, Thaisz J, Yehia G, Molina CA, Yatani A, Vatner DE, Vatner SF , Sadoshima J . Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest 2003 111:1463-1474.

Okumura S, Takagi G, Kawabe J, Yang G, Lee MC, Hong C, Liu J, Vatner DE, Sadoshima J , Vatner SF , Ishikawa Y. Disruption of type 5 adenylyl cyclases gene preserves cardiac function against pressure overload. PNAS. 2003 100:9986-9990.

Yamamoto M, Yang G, Hong C, Liu J, Holle E, Yu X, Wagner T, Vatner SF , Sadoshima J . Inhibition of thioredoxin in the heart increases oxidative stress and cardiac hypertrophy. J Clin Invest 2003 112:1395-1406.

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.

Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF , Sadoshima J . Sir2 a , a longevity factor and a class III histone decetylase, is an essential endogenous inhibitor of apoptosis in cardiac myocytes. Circ Res. 2004 95:971-980.

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.

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.

Yan L, Vatner DE, Kim SJ, Ge H, Masurekar M, Massover WH, Yang G, Matsui Y, Sadoshima J , Vatner SF . Autophagy in chronically ischemic myocardium. PNAS . 2005 102:13807-13812.

Zhai P, Yamamoto M, Galeotti J, Liu J, Masurekar M, Thaisz J, Irie K, Yu X, Kupershmidt S, Roden, DM, Yatani A, Vatner DE, Vatner SF , Sadoshima J .  Cardiac-specific overexpression of AT1 receptor mutant lacking G a q/G a i coupling causes hypertrophy and bradycardia in transgenic mice. J Clin Invest . 2005 115:3045-3056.

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.   

Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF , Sadoshima J . Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007 100:1512-1521.

Peter PS, Brady JE, Yan L, Chen W, Engelhardt S, Wang Y, Sadoshima J , Vatner SF , Vatner DE. Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta 2-adrenergic receptor, but not beta 1-adrenergic receptor. J Clin Invest. 2007 117:1335-1343.

Yan L, Vatner DE, O'Connor JP, Ivessa A, Ge H, Chen W, Hirotani S, Ishikawa Y, Sadoshima J , Vatner SF . Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects against Stress. Cell. 2007 130:247–258.

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.

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.