Chu-Huang (Mendel) Chen, M.D.,Ph.D.
Positions:
- Associate Professor of Medicine
- Clinical Director, Behavioral Medicine Research Center
Contact Information:
Phone: 713-798-4217
Fax: 713-798-4121
E-mail: cchen@bcm.edu
Basic Research Interests:
Dr. Chen and his associates have demonstrated that a novel atherogenic, electronegative low-density lipoprotein (LDL) subfraction can inhibit angiogenesis and induce apoptosis in vascular endothelial cells by inhibiting the transcription of fibroblast growth factor 2 (FGF2). The main goal of their research now is to identify the active lipid components of this electronegative LDL species. Using high-performance liquid chromatography and mass spectrometry, they are characterizing the discrete components of phospholipids and neutral lipids isolated exclusively from this particular LDL species. To determine the plasma membrane receptors responsible for transducing the signals of this electronegative LDL and its active components, Dr. Chen's team is testing a novel sequential receptor model that involves the platelet-activating factor and leptin-like oxidized LDL receptors. To inhibit the translation of these receptors, small interfering RNAs against each gene have been generated. In many cell types, FGF2 activates phosphatidyl 3'-kinase (PI3K), which in turn activates protein kinase Akt. Dr. Chen has demonstrated a novel FGF2-PI3K-Akt autoregulatory loop in vascular endothelial cells. To delineate the intracellular signaling pathways, Dr. Chen's team is examining the interactions between the FGF2-PI3K-Akt loop and other apoptosis regulatory systems. Several cell lines have been established to study these mechanisms. The goal is to fully characterize a novel atherogenic and proinflammatory LDL species. These studies will provide the basis for development of new therapeutic strategies aimed at the plasma, cell membrane receptors, and genes that are activated by this atherogenic lipid.
Clinical Research Interests:
Electronegative LDL and Heart
At the American College of Cardiology Scientific Sessions 2004, Dr. Chen presented work demonstrating that the aforementioned electronegative LDL species is a novel atherogenic lipoprotein independent of other risk factors and that compliance to statin treatment can effectively reduce its abundance in patients with hypercholesterolemia. The current clinical foci of their study are threefold: 1) epidemiological analysis of plasma concentrations of this electronegative LDL species in patients with obesity or metabolic syndrome, 2) determination of whether electronegative LDL plays a role in acute coronary syndromes and destabilization of vulnerable plaques, 3) determination of whether the excessive abundance of this LDL species is related to increased left ventricular mass, which is a risk factor of sudden cardiac death.
Tai Chi and Heart
Tai Chi exercise has long been considered to the beneficial to be cardiovascular system, but scientific studies at the cell level have not been reported. There are several different styles of Tai Chi, but all of them originated from the Chen style. As Medical Director of the USA Chen Tai Chi Federation, Dr. Chen and his associates will conduct studies to link the clinical benefits of Tai Chi exercise to cardiovascular disease prevention. One of the goals is to determine the effect of Tai Chi on electronegative LDL reduction and subsequent endothelial cell protection in patients with metabolic syndrome.
Selected Publications:
- Lu J, Yang JH, Burns AR, Chen HH, Tang D, Walterscheid JP, Suzuki S, Yang CY, Sawamura T, Chen CH. Mediation of electronegative LDL signaling by LOX-1: A possible mechanism of endothelial apoptosis. Circ Res. 2009;104:619-627.
- Chang PY, Lu SC, Lee CM, Chen YJ, Dugan TA, Huang WH, Chang SF, Liao WS, Chen CH, Lee YT. Homocysteine inhibits arterial endothelial cell growth through transcriptional downregulation of fibroblast growth factor-2 involving G protein and DNA methylation. Circ Res 2008;102:933-941.
- Lu J, Jiang W, Yang JH, Chang PY, Walterscheid JP, Chen HH, Marcelli M, Tang D, Lee YT, Liao WS, Yang CY, Chen CH.Electronegative LDL impairs vascular endothelial cell integrity in diabetes by disrupting FGF2 autoregulation. Diabetes 2008;57:158-166.
- Tang D, Lu J, Walterscheid JP, Chen HH, Engler DA, Sawamura T, Chang PY, Safi HJ, Yang CY, Chen CH.Electronegative LDL circulating in smokers impairs endothelial progenitor cell differentiation by inhibiting Akt phosphorylation via LOX-1. J Lipid Res 2008;49:33-47.
- Yang CY, Chen HH, Huang MT, Raya JL, Yang JH, Chen CH, Gaubatz JW, Pownall HJ, Taylor AA, Ballantyne CM, Jenniskens FA, Smith CV. Pro-apoptotic low-density lipoprotein subfractions in type II diabetes. Atherosclerosis 2007;193:283-91.
- Cheng J, Cui R, Chen CH, Du J. Oxidized low-density lipoprotein stimulates p53-dependent activation of proapoptotic Bax leading to apoptosis of differentiated endothelial progenitor cells. Endocrinology 2007;485:2085-2094
- Chen CH, Walterscheid JP. Plaque angiogenesis versus compensatory arteriogenesis in atherosclerosis. Circ Res 2006;99:787-789.
- Chen CH. Platelet-activating factor acetylhydrolase: is it good or bad for you? Curr Opin Lipidol 2004;15:337-341.
- Chen CH, Poucher SM, Lu J, Henry PD. Fibroblast growth factor 2: from laboratory evidence to clinical application. Curr Vasc Pharmacol 2004;2:33-43. Figure selected for cover image
- Chang PY, Lu SC, Su TC, Chou SF, Huang WH, Morrisett JD, Chen CH, Liau CS, Lee YT. Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation. J Lipid Res 2004;45:2116-2122.
- Chen CH, Jiang T, Yang JH, Jiang W, Lu J, Marathe GK, Pownall HJ, Ballantyne CM, McIntyre TM, Henry PD, Yang CY. Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation 2003;107:2102-2108.
- Yang CY, Raya JL, Chen HH, Chen CH, Abe Y, Pownall HJ, Taylor AA, Smith CV. Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler Thromb Vasc Biol 2003;23:1083-1090.
- Chang PY, Luo S, Jiang T, Lee YT, Lu SC, Henry PD, Chen CH. Oxidized low-density lipoprotein downregulates endothelial basic fibroblast growth factor through a pertussis toxin-sensitive G-protein pathway: mediator role of platelet-activating factor-like phospholipids. Circulation 2001;104:588-593.
- Chen CH, Jiang W, Via DP, Luo S, Li TR, Lee YT, Henry PD. Oxidized low-density lipoproteins inhibit endothelial cell proliferation by suppressing basic fibroblast growth factor expression. Circulation 2000;101:171-177.