Jian-Xiong Chen, MD, FAHA
Department of Pharmacology and Toxicology
University of Mississippi Medical Center
Room G325, Jackson, MS, 39216, USA
After receiving the M.D. and a master’s degree in pharmacology from Central South University of China, Dr. Chen completed his postdoctoral training in pathology at Vanderbilt University Medical Center. Dr. Chen served as an assistant professor in Pathology, and became associate professor of Pediatrics at Vanderbilt University from 2002-2010. He joined the University of Mississippi Medical Center as an associate professor at Department of Pharmacology and Toxicology in 2011-present. Dr. Chen is Fellow of American Heart Association (AHA) and member of American Physiology Society. Dr. Chen has served as a grant reviewer committee of NIH, AHA and British Medical Research Council. During the past 12 years, Dr. Chen has been a part of a very successful research team that have been well-funded by NIH and AHA. He is the author of 40 peer-reviewed publications and is currently funded by National Heart, Lung and Blood Institute. The long-term goals of his laboratory research are to understand the pathogenesis and identify the intracellular molecular basis that may contribute to abnormal angiogenesis and regeneration, exacerbation of cardiac dysfunction and heart failure, then, to develop novel therapies that can prevent or reverse these devastating diabetic cardiovascular diseases.
His research interests include: Oxidants and angiogenesis, angiogenic factors gene therapy on diabetic impaired angiogenesis, myocardial regeneration and bone marrow/stem cell differentiation.
The long-term goals of my laboratory research are to identify the intracellular molecular basis that may contribute to diabetes-associated impairment of angiogenesis and regeneration, exacerbation of cardiac dysfunction and heart failure, then, to develop novel therapies that can prevent or reverse these devastating diabetic cardiovascular diseases. Specifically, my laboratory research interesting is focused on: The receptor tyrosine kinase (RTK) angiopoietins/Tie-2 system,prolyl hydroxylases-2 (PHD2), apelin/APJ and Notch signaling interactions in the regulation of vascular smooth muscle maturation, capillary growth and regression, cardiac hypertrophy and heart failure. By using genetic modified Notch3 knockout, conditional knockout of PHD2 diabetic mice model, myocardial ischemia-induced angiogenesis in vivo and in vitro angiogenesis models, we will define: (1) the molecular mechanisms by which hyperglycemia or diabetes disrupt angiopoietins/Tie-2 system and cause vessel immaturation and regression; (2) their interactive effects with PHD2/HIF-1a signaling and apelin/APJ on myocardial neovessel maturation and angiogenesis; (3) the mechanisms by which hyperglycemia interferes with pro-inflammatory programme of endothelial cell with a focus on the role of elevated Ang-2; and (4) whether disruption of Jagged1/Notch3 contributes to diabetes-induced abnormal vascular smooth muscle maturation, vascular progenitor differentiation and facilitate adverse cardiac remodeling and heart failure in diabetes. Identify novel molecular basis as a potential therapeutic target in diabetic cardiac hypertrophy and fibrosis will provide novel approaches to prevent and/or reverse diabetic myocardial ischemia disease.
• Member of American Heart Association
• Member of American Physiological Society
2008: July 23; invited talk, Beijing University Medical Center, Beijing, PR China, Title: NADPH oxidase and diabetic angiogenesis.
2010: May 4, invited talk, University of Missouri, Department of Pharmacology and Physiology, Columbia, MO. Title Angiopoietins/Tie-2 system and diabetic abnormal angiogenesis.
2010: July 12, invited talk, University of Mississippi Health Center, Department of Pharmacology, Jackson, MS. Title “Angiopoietins/Tie-2 system in diabetic vascular complications”.
2011 March 16, invited talk, University of Mississippi Health Center, Department of Physiology& Biophysics, Jackson, MS. Title “Angiopoietins/Tie-2 in diabetic infarcted heart”.
2011 November 4, invited talk, University of Southern Mississippi, Department of Biological Science, Hattiesburg, MS. Title “Angiopoietins/Tie-2 system in diabetic complications”.
2012 December 11, invited talk, University of Mississippi Medical Center, Department of Biochemical Science, Jackson, MS. Title “Mechanisms of impairment of myocardial angiogenesis in type II diabetes”.
1. Liao DF, Yu L, Chen JX. A new method to study correlation between endothelium damage and free rardicals-morphology change of endothelium under scanning electron microscopy. Journal of Hengyang Medical College. 1992; 20(4): 341-343.
2. Chen JX, Yu L, Liao DF, Cao JG, Zhu BY. The effect of oxygen free radicals on airway of guinea pig and its mechanism. Journal of Hengyang Medical College. 1993; 21(4): 360-362.
3. Chen JX, Yu L, Liao DF, et al. Protective effect of gypenosides on free radical injury in isolated guinea pig heart. Journal of Hengyang Medical College. 1993; 21(3): 243-245.
4. Wan Y, Weng SA, Chen JX, Wu HX, Cao YS. Effects of estradiol on asthma of guinea pigs and its relationship to beta-adrenergic receptors. Chinese Pharmacological Bulletin. 1993, 9(4): 295-297.
5. Chen JX, Wu HX, You W. The role of endotoxin in the bronchial hyper-reactivity formation. National Medical Journal of China. 1994; 74(1): 38-40.
6. Chen JX, Cao YS. Protection ammonium glycyrrhizanate against endotoxin-induced bronchial hyperreactivity. Chinese Journal of Pharmacology and Toxicology. 1994; 8(3): 235-236.
7. Chen JX, Cao YS. Effect ammonium glycyrrhizanate against endotoxin-induced bronchial hyperreactivity-in relation to beta-cAMP system. Chinese Traditional and Herbal Drugs. 1994; 1(1): 17-18.
8. Xiao GL, Liao DF, Chen JX, Yu L. Protective effect of gypenosides on OFR-induced damage of relaxing capacity of rabbit thoracic aortae in vitro. Chinese Pharmacological Bulletin. 1994; 10(2): 136-138.
9. Chen JX, Tang XQ, Zhu BY, Liao DF. The mechanism of exogenous oxygen free radicals induced vasospasm of isolated basilar artery. Chinese Journal Arteriosclerosis. 1994; 2(2): 88-91.
10. Liao DF, Chen JX, Huang HL, Tang XQ, Cao JG, Yu L. Correlation bwteen the protection of probucol on injury of endothelial cells by free radicals and the activity of nitric oxide. Chinese Journal Arteriosclerosis. 1994; 2(2): 67-71.
11. Chen JX, Liao DF, Yu L, Xiao GL, Zhu BY, Tang XQ. Protective effect of captopril on electrolyzed perfusion solution induced vasospasm of isolated basilar artery. Chinese Journal of Pharmacology and Toxicology. 1995; 9(1): 44-46.
12. Li LX, Yu L, Chen JX, et al. Oxidized low density lipoprotein promotion of adhesion of monocytes to endothelial cells in vitro. Chinese Journal Arteriosclerosis. 1996; 4(4): 272-275.
13. Chen JX, Liao DF, Tang XQ, Yu L, Zeng H, Cao JG. Protection of Gypenosides against oxygen free radical induced vasospasm of isolated rabbit basilar artery. Chinese Traditional and Herbal Drugs. 1997, 28(4): 219-221.
14. Huang HL, Chen JX, Zeng H et al. Oxygen free radicals stimulates epithelial-leukocyte adhesion. Journal of Hengyang Medical College. 1996; 24(4): 255-257.
15. Chen JX, Zeng H, Zhu BY. Effect of endotoxin on Endothelin-1, Thromboxane A2 and prostaglandin E2 secretion and role of oxygen free radicals. Journal of Hengyang Medical College. 1998; 26(8): 121-123. 16.
16. Liao DF, Lu N, Lei LS, Yu L, Chen JX. Effects of gypenosides on mouse splenic lymphocyte transformation and DNA polymerase II activity in vitro. Acta Pharmacological Sin. 1995; 16(4): 322-4.
17. Chen JX, Chen WZ, Hung HL, Chen LX, Xie ZZ, Zhu PY. Protective effects of Ginkgo biloba extract against lysophosphatidylcholine induced endothelium cell damage. Acta Pharmacological Sin. 1998; 19(4): 359-363.
18. Li LX, Chen JX, Liao DF, Yu L. Probucol inhibits oxidized-low density lipoprotein induced adhesion of monocytes to endothelial cells by reducing P-selectin synthesis in vitro. Endothelium. 1998; 6: 1-8.
19. Su CY, Chong KY, Chen JX, Ryter SW, Lai CC. A physiological relevant hyperthermia selectively activates constitutive Hsp70 in H9c2 cardiac myoblasts and confers oxidative protection. J Mol Cell Cardiol. 1999; 31: 845-855.
20. Chen JX, Zeng H, Chen X, Su CY, Lai CC. Induction of heme oxygenase-1 by Ginkgo biloba extract but not its tepernoids constituents partially mediated its protective effect against lysophosphatidylcholine-induced damage. Pharmacological Research. 2001; 43(1): 63-69.
21. Chen JX, Berry LC, Christman BW, Tanner M, Myers PR, Meyrick BO. NO regulates LPS-stimulated cyclooxygenase gene expression and activity in pulmonary artery endothelium. Am J Physiology. 2001; 280: L450-457.
22. Chen JX, Berry LC, Tanner M, Myers PR, Meyrick BO. Nitric oxide donors regulate nitric oxide synthase in bovine pulmonary artery endothelium. J Cellular Physiology. 2001; 186: 116-123.
23. Chen JX, Berry LC, Meyrick BO. Glutathione mediates LPS-stimulated COX-2 expression via early transient P42/44 activation. J Cellular Physiology. 2003; 197: 86-93.
24. Chen JX, Lawrence ML, Cunningham G, Christman BW, Meyrick B. Hsp90 and Akt Modulate Ang-1 Induced Angiogenesis via NO in Coronary Artery Endothelium. J Appl Physiol. 2004; 96: 612-620.
25. Chen JX, Meyrick BO. Hypoxia Increases Hsp90 Binding to eNOS via a PI3 Kinase-Akt Pathway in Porcine Coronary Artery Endothelium. Lab Invest. 2004; 84(2): 182-190.
26. Chen JX, Chen Y, DeBusk L, Lin W, Lin PC. Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis. Am J Physiol Heart Circ Physiol. 2004; 287(1): H187-95.
27. Pei J, Yan PK, Chen JX, Zhu BY, Lei XY, Yin WD, Liao DF. High-density lipoprotein 3 inhibits oxidized low- density lipoprotein-induced apoptosis via promoting cheolesterol efflux in RAW264.7 cells. Acta Pharmacological Sin. 2006; 27(2): 151-7.
28. Chen JX, Zeng H, Lawrence ML, Sadikot RT, Blackwell TS, Meyrick B. Role of NADPH oxidase-derived reactive oxygen species (ROS) in angiopoietin-1-induced angiogenesis. Am J Physiol Heart Circ Physiol. 2006; 291: 1563-1572.
29. Chen JX, Zeng H, Qin-Hui Tuo, Heidi Yu, Meyrick B, Judy Aschner. NADPH oxidase mediates myocardial Akt, ERK1/2 activation and angiogenesis after hypoxia/reperfusion. Am J Physiol Heart Circ Physiol. 2007; 292: H1664-1674.
30. Tuo QH, Zeng H, Stinnett A, Yu HD, Aschner JL, Chen JX. Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Am J Physiol Heart Circ Physiol. 2008; 294(6): H2547-57
31. Chen JX, Stinnett A. Disruption of Ang-1/Tie-2 signaling contributes to the impaired myocardial vascular maturation and angiogenesis in type II diabetic mice. Arterioscler Thromb Vasc Biol. 2008; 28: 1606-1613. doi: 10.1161/ATVBAHA.108.169235.
32. Chen JX, Stinnett A. Critical role of the NADPH oxidase subunit p47phox on vascular TLR expression and neointimal lesion formation in high fat diet-induced obesity. Lab Invest. 2008; 88: 1316-1328. doi: 10.1038/labinvest.2008.92.
33. Chen JX, Stinnett A. Ang-1 gene therapy inhibits hypoxia-inducible factor-1alpha (HIF-1alpha)-prolyl-4-hydroxylase-2, stabilizes HIF-1alpha expression, and normalizes immature vasculature in db/db mice. Diabetes. 2008; 57(12): 3335-43. doi: 10.2337/db08-0503.
34. Tuo QH, Xiong GZ, Zeng H, et al. Angiopoietin-1 protects myocardial endothelial cell function blunted by angiopoietin-2 and high glucose condition. Acta Pharmacol Sin. 2011; 32(1): 45-51. doi: 10.1038/aps.2010.183.
35. Chen JX, Tuo QH, Liao DF, Zeng H. Inhibition of protein tyrosine phosphatase improves impaired angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes. Experimental Diabetes Research. 2012; 2012: 836759 doi: 10.1155/2012/836759.
36. Chen JX, Zeng H, Reese J, Aschner JL, Barbara Meyrick. Overexpression of angiopoietin-2 impairs myocardial angiogenesis and exacerbates cardiac fibrosis in the diabetic db/db mouse model. Am J Physiol Heart Circ Physiol . 2012; 302(4): H1003-12. doi: 10.1152/ajpheart.00866.2011
37. Zeng H, Li L, Chen JX. Overexpression of Angiopoietin-1 increases CD133+/c-kit+ cells and reduces myocardial apoptosis in db/db mouse infarcted hearts. PLoS One. 2012; 7(4): e35905. doi: 10.1371/journal.pone.0035905.
38. Chen JX, OMara PW, Poole SD, et al. Isoprostanes as physiological mediators of transition to newborn life: Novel mechanisms regulating patency of the term and preterm ductus arteriosus. Pediatric Research. 2012; 72: 122-128.
39. Li L, Zeng H, Chen JX. Apelin-13 increases myocardial progenitor cells and improves repair of post-myocardial infarction. Am J Physiol Heart Circ Physiol. 2012: 303 (5): H605-18. doi: 10.1152/ajpheart.00366.2012.
40. Li L, Zeng H, Hou X, He X, Chen JX. Myocardial Injection of Apelin-Overexpressing Bone Marrow Cells Improves Cardiac Repair via Upregulation of Sirt3 after Myocardial Infarction. PLoS ONE. 2013; 8(9): e71041. doi: 10.1371/journal.pone.0071041.
41. Zeng H, He X, Hou X, Li L, Chen JX. Apelin gene therapy increases myocardial vascular density and ameliorates diabetic cardiomyopathy via upregulation of Sirtuin 3. Am J Physiol Heart Circ Physiol. 2014; 306: H585-H597. doi: 10.1152/ajpheart.00821.2013.
42. Hou X, Zeng H, Tuo Q-H, Liao D-F, Chen J-X. Apelin gene therapy increases autophagy via activation of sirtuin 3 in diabetic heart. Diabetes Res Open J. 2015; 1(4): 84-91. doi: 10.17140/DROJ-1-115