Chengwen Sun, M.D., Ph.D.
8B2 Sudro Hall
Office Phone: 701.231.6454
Lab Phone: 701.231.9403
1983-1988: M.D. Medicine, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin.
1990-1996: Ph.D. Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin.
1996-2000: Postdoctoral Fellow, Dept of Physiology, Medical College of Wisconsin, Milwaukee, WI.
2000-2005: Postdoctoral Associate, Dept of Physiology, University of Florida, Gainesville, FL.
Our research group focuses on central blood pressure regulation and pathogenesis of hypertension to identify novel targets for the treatment of hypertension and other cardiovascular diseases. Then, based on the molecular structures of these target proteins, we develop pharmaceutical and gene-therapeutic tools for the clinical use in the treatment of these diseases.
The first target we are studying is angiotensin-converting enzyme 2 (ACE2), a novel zinc metalloprotease that cleave Angiotensin II to form Ang (1-7). Previous studies have demonstrated that Ang (1-7) has protective effect on the cardiovascular system and antagonize the action of Ang II via a PTEN-dependent mechanism. It is well-known that Ang II plays an important role in the pathogenesis of cardiovascular diseases. Several Ang II-targeting drugs have been used in the clinics and proven effective in the prevention and the treatment of cardiovascular diseases, such as AT1 receptor antagonists by blockade Ang II action, ACE inhibitors by decease of Ang II production. Here, we are targeting ACE2 to increase Ang II degradation lowering Ang II levels.
The second project we are working on is to study apelin-APJ system in the central control of blood pressure and cardiovascular function. Apelin is an endogenous ligand for the G-protein coupled angiotensin I-like receptor (APJ). Previous studies from our group and others have demonstrated that expression of apelin in the brain cardiovascular regulatory areas is enhanced in several hypertensive animal models and that microinjection of apelin-13 or overexpression of preproapelin in these brain areas results in a significant increase in blood pressure, associated with cardiac hypertrophy and fibrosis. Based on these studies, we hypothesis that increased expression of apelin in the brain cardiovascular regulatory areas contributes to the development of hypertension and related cardiovascular complications. The aim of our current study is to investigate the role of apelin in the cardiovascular regulation and in the pathogenesis of cardiovascular diseases using selective silencing apelin expression with lentiviral vector-mediated shRNA in normotensive and hypertensive rat models.
Another research project is to identify the biofunction of NOS1AP in the brain and in the heart. Human genetic studies demonstrated that variants of NOS1AP, nitric oxide synthase 1 (a neural isoform) adaptor protein, locus are strongly related to QT interval prolongation and sudden cardiac death (SCD). We have observed that this protein is highly expressed in brain cardiovascular regulatory areas of rats. Thus, the aim of our project is to study the role of NOS1AP in the control of cardiac function and to identify mechanisms by which dysfunction of this protein causes QT interval prolongation and sudden cardiac death.
- Bao Y, Wang X, Li W, Huo D, Shen X, Han Y, Tan J, Zeng Q, Sun C. 20-HETE Induces Apoptosis in Neonatal Rat Cardiomyocytes through Mitochondrial-dependent Pathways. J Cardiovasc Pharmacol. 2011 Mar;57(3):294-301.
- Yao F, Modgil A, Zhang Q, Pingili A, Singh N, O'Rourke ST, Sun C. Pressor effect of apelin-13 in the rostral ventrolateral medulla: role of NAD(P)H oxidase-derived superoxide. J Pharmacol Exp Ther. 2011 Feb;336(2):372-80.
- Tunstall RR, Shukla P, Grazul-Bilska A, Sun C, O'Rourke ST. MT2 receptors mediate the inhibitory effects of melatonin on nitric oxide-induced relaxation of porcine isolated coronary arteries. J Pharmacol Exp Ther. 2011 Jan;336(1):127-33.
- Zeng Q, Han Y, Bao Y, Li W, Li X, Shen X, Wang X, Yao F, O'Rourke ST, Sun C. 20-HETE increases NADPH oxidase-derived ROS production and stimulates the L-type Ca2+ channel via a PKC-dependent mechanism in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1109-17.
- Yao FR, Sun CW, Chang SK. Morton lentil extract attenuated angiotensin II-induced cardiomyocyte hypertrophy via inhibition of intracellular reactive oxygen species levels in vitro. J Agric Food Chem. 2010 Oct 13;58(19):10382-8.
- Sun C, Zubcevic J, Polson JW, Potts JT, Diez-Freire C, Zhang Q, Paton JF, Raizada MK. Shift to an involvement of phosphatidylinositol 3-kinase in angiotensin II actions on nucleus tractus solitarii neurons of the spontaneously hypertensive rat. Circ Res. 2009 Dec 4;105(12):1248-55.
- Zhang Q, Yao F, O'Rourke ST, Qian SY, Sun C. Angiotensin II enhances GABA(B) receptor-mediated responses and expression in nucleus tractus solitarii of rats. Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1837-44.
- Yu Q, Purwaha P, Ni K, Sun C, Mallik S, Qian SY. Characterization of novel radicals from COX-catalyzed arachidonic acid peroxidation. Free Radic Biol Med. 2009 Sep 1;47(5):568-76.
- Zhang Q, Yao F, Raizada MK, O'Rourke ST, Sun C. Apelin gene transfer into the rostral ventrolateral medulla induces chronic blood pressure elevation in normotensive rats. Circ Res. 2009 Jun 19;104(12):1421-8.
- Zeng Q, Zhou Q, Yao F, O'Rourke ST, Sun C. Endothelin-1 regulates cardiac L-type calcium channels via NAD(P)H oxidase-derived superoxide. J Pharmacol Exp Ther. 2008 Sep;326(3): 732-8.
- Yao F, Sumners C, O'Rourke ST, Sun C. Angiotensin II increases GABAB receptor expression in nucleus tractus solitarii of rats. Am J Physiol Heart Circ Physiol. 2008 Jun;294(6): H2712-20.