Chunxiang Zhang, M.D., Ph.D., Associate Professor in Surgery
   Director, Vascular Injury Core Laboratory

According to the American Heart Association, atherosclerosis is the leading cause of death in the United States and the cause of more than half of all mortality in the world's developed countries. Neointima formation is a crucial initial step in the development of atherosclerosis. The central hypothesis of our research is that the phospholipid growth factor lysophosphatidic acid (LPA), generated in minimally oxidized low-density lipoprotein (mox-LDL) elicits neointima formation through the activation of the Peroxisome Proliferator Activating Receptor gamma (PPAR-gamma). To date we have found that application of LPA or the PPAR-gamma specific agonist Rosiglitasone into the rat carotid artery elicits robust neointima formation within a week. This response is not mediated by plasma membrane receptors for LPA but is blocked by GW GW9662, a specific inhibitor of PPAR-gamma.

Future studies will focus on characterizing LPA-induced neointima formation and elucidating the role of PPAR-gamma as well as determining the role of PPAR-gamma in neointima formation induced by mox-LDL.

Recent Manuscripts

Short-term administration of basic fibroblast growth factor enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction. Zhang C, Yang J, Feng J and Jennings LK. J Lab Clin Med 140(2):119-25. 2002.

Interaction of MPO with vascular NAD(H)P oxidases derived ROS in the vascular wall and its roles in vascular diseases. Zhang C, Jacobs JD and Jennings LK. Circulation 106(19):11-16, 2002.

Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR and Freeman BA. Science 296(5577):2391, 2002.

Short-term administration of basic fibroblast growth factor enhance enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction. Zhang C, Yang J, Feng J, Jennings LK. J Lab Clin Med. 2002; 140(2):119-125.

Interaction of MPO with vascular NAD(H)P oxidases derived ROS in the vascular wall and its roles in vascular diseases. Zhang C, Yang J, Jacobs JD, Jennings LK. Am J Physiol Heart Circ Physiol. 2003;285: H2563-H2572.

Vascular endothelial growth factor gene delivery for revascularization in transplanted human islets. Ajit S. Narang AS, Chen K, Henry J, Zhang C, Sabek O, Fraga D, Kotb M, Gaber O, Mahato RI. Pharm Res. 2004; 21:15-25.

Increase of protein tyrosine phosphatase levels in vascular injury and in cultured aortic smooth muscle cells treated with specific growth factors. Chang Y, Zhuang D, Zhang C, Hassid A. Am J Physiol Heart Circ Physiol. 2004;287(5):H2201-8.

Adenovirus-based vascular endothelial growth factor gene delivery to human pancreatic islets. Cheng K, Fraga D, Zhang C, Kotb M, Gaber AO, Guntaka RV, Mahato RI. Gene Ther. 2004; 11:1105-1116.

Attenuation of neointima formation through the inhibition of DNA repair enzyme PARP-1 in the rat carotid artery injury model. Zhang C, Yang J, Jennings LK. Am J Physiol Heart Circ Physiol. 2004;287(2):H659-66.

Lysophosphatidic acid induces neointima formation through PPARg. Zhang C, Baker DL,Yasuda S, Makarova N, Johnson LR, Balazs L, Marathe G, McIntyre TM, Xu Y, Prestwich GD, Bittman R, Tigyi G. J Exp Med. 2004 Mar 15;199(6):763-74.

Leukocyte-derived myeloperoxidase amplifies high glucose-induced vascular dysfunction through the interaction with high glucose stimulated, vascular nonleukocyte-derived reactive oxygen species. Zhang C, Yang J, Jennings LK. Diabetes. 2004;53(11):2950-9.

Contribution of arachidonic acid metabolites derived via cytochrome P4504A to angiotensin II-induced neointimal growth. Yaghini FA, Zhang C, Parmentier JH, Estes AM, Jafari N, Schaefer SA, Malik KU. Hypertension. 2005;45:1182-7.

The morphological and functional alterations of the cochlea in apolipoprotein E deficient mice. Guo Y, Zhang C, Nair U, Du X, Yoo TJ. Hear Res. 2005;208:54-67.

Regulation of Vascular Smooth Muscle Cell Proliferation and Migration by Human Sprouty 2. Zhang C, Chaturvedi D, Jaggar L, Magnuson D, Lee JM, Patel TB. Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):533-8.

Blockade of nuclear factor of activated T cells activation signaling suppresses balloon injury-induced neointima formation in a rat carotid artery model. Liu Z, Zhang C (Co-first author), Dronadula N, Li Q, Rao GN. J Biol Chem. 2005;280(15):14700-8.

Ang II-Induced Neointimal Growth is Mediated via cPLA2 and PLD2 activated Akt in balloon-injured rat Carotid Artery. Fang L, Zhang C, Schaefer S, Eates A, Malik KU. Am J Physiol Heart Circ Physiol. 2005 05 Dec;289 (6):H2592-601.

Counter-Regulatory Function of PTP1B in Platlet-Derived Growth Factor- or Fibroblast Growth Factor-Induced Motility and Proliferation of Cultured Smooth Muscle Cells and in Neointima Formation. Chang Y, Ceacareanu B, Zhuang D, Zhang C, Pu Q, Ceacareanu AC, Hassid A. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):501-7.

L-arginine chlorination results in the formation of a nonselective nitric oxide synthase inhibitor. J Pharmacol Exp Ther. Yang J, Ji R, Cheng Y, Sun JZ, Jennings LK and Zhang C. 2005. J Pharmacol Exp Ther. 2006 May 22. [Epub ahead of print]

 

 

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