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Brent A. French

Associate Professor of Biomedical Engineering, Radiology and Medicine

Ph.D., Biochemistry, Louisiana State University, 1987

UVA Health System
Box 800759
Charlottesville, VA 22908

bf4g@virginia.edu

Research Interests

1. Interplay of Nitric Oxide with Superoxide in Health and Disease

The basic research focus of our laboratory is to determine the physiological significance of the balance that exists between nitric oxide and superoxide in the cardiovascular systems of higher mammals. Recent investigations indicate that this balance becomes critical in the setting of heart attack. Nitric oxide and superoxide are free radicals that react spontaneously to form peroxynitrite, a very destructive reactive oxygen species. Basic research efforts in the laboratory are focused on determining the roles played by nitric oxide, superoxide and peroxynitrite in both the acute and chronic settings of myocardial infarction.

2. Novel Therapies for Cardioprotection and Cardiopreservation

The applied research focus of the laboratory is to develop novel therapies to protect the intact mammalian heart against myocardial infarction and heart failure. An interdisciplinary approach is used to integrate recent advances in molecular biology with cutting-edge imaging techniques such as MRI and echocardiography to expedite research by accurately measuring the effect of novel therapies on cardiovascular disease. Accurate animal models of myocardial stunning, infarction and left ventricular remodeling after myocardial infarction have been implemented in rabbits, rats and mice. Using direct gene transfer techniques in these models, we have previously shown that either superoxide dismutase or nitric oxide synthase can provide the heart with substantial protection against myocardial infarction (i.e., reduce the extent of myocardial infarction by > 50%). Recently, the excess production of superoxide and nitric oxide have also been implicated in the progressive loss of cardiac function that characterizes heart failure after myocardial infarction. Thus we anticipate that gene therapy with superoxide dismutase may also prove beneficial in the setting of left ventricular remodeling after myocardial infarction by reducing the formation of peroxynitrite and thereby controlling oxidative damage in the heart and vasculature.

Selected Publications

Berr SS, Xu Y, Roy RJ, Kundu B, Williams MB, French BA. Serial multimodality assessment of myocardial infarction in mice using magnetic resonance imaging and micro-positron emission tomography provides complementary information on the progression of scar formation. Circulation. 115(2007)e428-9.

Prasad KM, Xu Y, Yang Z, Toufektsian MC, Berr SS, French BA. Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Molecular Therapy. 15(2007)764-71.

Young AA, French BA, Yang Z, Cowan BR, Gilson WD, Berr SS, Kramer CM, Epstein FH. Reperfused myocardial infarction in mice: 3D mapping of late Gd enhancement and strain. J. Card. Mag. Res. 8(2006)685-92.

French BA, Li Y, Klibanov AL, Yang Z, Hossack JA. 3D perfusion mapping in post-infarct mice using myocardial contrast echocardiography. Ultrasound in Medicine & Biology. 32(2006)805-15.

Yang Z, Day YJ, Toufektsian MC, Xu Y, Ramos SI, Marshall MA, French BA, Linden J. Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to action on CD4+ T lymphocytes. Circulation 114 (2006)2056-64.

Xu Y, Huo Y, Toufektsian MC, Ramos SI, Ma Y, Tejani AD, French BA, Yang Z. Activated platelets contribute importantly to myocardial reperfusion injury. Amer. J Physiology - Heart & Circ. Phys. 290(2006):H692-9.

Toufektsian MC, Yang Z, Prasad KM, Overbergh L, Ramos SI, Mathieu C, Linden J, French BA. Stimulation of A2A-adenosine receptors after myocardial infarction suppresses inflammatory activation and attenuates contractile dysfunction in the remote left ventricle. Amer. J. Physiology - Heart & Circ. Phys. 290(2006):H1410-8.

Gilson WD, Yang Z, French BA, Epstein FH. Measurement of myocardial mechanics in mice before and after infarction using multislice displacement-encoded MRI with 3D motion encoding. Amer. J. Physiology - Heart & Circ. Phys. 288(2005)H1491-1497.

Yang Z, Berr SS, Gilson WD, Toufektsian MC, French BA. Simultaneous evaluation of infarct size and cardiac function in intact mice by contrast-enhanced cardiac magnetic resonance imaging reveals contractile dysfunction in non-infarcted regions early after myocardial infarction. Circulation 109(2004)1161-1167.

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