| Boston Science Publishing

Name: Dr. Che Ping Cheng

Educational Qualification: M. D, Ph. D, FAHA

Designation: Director and Professor, Wake Forest University, USA.

Department: Internal Medicine

Email: ccheng@wakehealth.edu

Research Interests: Cardiovascular Physiology, Pharmacology, Internal Medicine and Molecular Biology.

BIOGRAPHY:

Dr. Cheng has broad background in cardiovascular physiology, pharmacology, and molecular biology with specific training and expertise in all the key aspects of the project. She is an established investigator in the field of CHF with primary focus on the modulation of left ventricular filling dynamics at rest and during exercise, the function significance of neurohormonal activation in CHF, adrenergic regulation in the setting of cardiomyopathies, as well as cardiac cellular [Ca2+]i regulation, signal transduction and energetics. She has extensive direct experience in the preparation and study of conscious instrumented animals (>25 years) performing sophisticated serial measurement of LV systolic and diastolic performance. In order to investigate the cellular and molecular mechanisms underlying our observations in conscious animals, she has developed the techniques to serially harvest myocytes before, during, and after the development of CHF from LV biopsies obtained from the same animals . As PI or co-Investigator on several previous university-, AHA- and NIH-funded grants, she has successfully completed several projects related functional significance of neurohormonal (including RAS and Beta-adrenergic activation before and as CHF progresses of several different animal models (including rat, mouse, dog and monkey). This proposal will directly address one of the most perplexing problems regarding the mechanism for the local formation of Ang II in cardiac tissue. The current grant application addresses the important problem of the impact of cardiovascular disease. Dr. Cheng has the expertise, training and motivation necessary to successfully carry out the proposed research project. In fact, Dr. Chengâ€™s knowledge and experience put her in a unique position to bring scientific insights to the proposed studies in this application.

PUBLICATIONS

1. Little WC, Cheng CP, Peterson T, Vinten-Johansen J. Response of the left ventricular end-systolic pressure-volume relation in conscious dogs to a wide range of contractile states. Circulation 1988; 78:736-745.

2. Little WC, Cheng CP, Mumma M, Igarashi Y, Vinten-Johansen J, Johnston WE. Comparison of measures of left ventricular contractile performance derived from pressure-volume loops in conscious dogs. Circulation 1989; 80:1378-1387.

3. Cheng CP, Freeman GL, Santamore WP, Constantinescu MS, Little WC. Effect of loading conditions, contractile state and heart rate on early diastolic left ventricular filling in conscious dogs. Circ Res 1990; 66:814-823.

4. Cheng CP, Shihabi Z, Little WC. Acute effects of mildly intoxicating levels of alcohol on left ventricular function in conscious dogs. J Clin Invest 1990; 85:1858-1865.

5. Applegate RJ, Cheng CP, Little WC. Simultaneous conductance catheter and dimension assessment of left ventricle volume in the intact animal. Circulation 1990; 81:638-648.

6. Glantz SA, Boltwood CM, Appleyard RF, Applegate RT, Cheng CP, Little WC. Volume conductance catheter. (Letter to Editor about Circulation 1990; 81(2):703-706) Circulation 1990; 81(6):2028.

7. Little WC, Cheng CP. Left ventricular-arterial coupling in conscious dogs. Am J Physiology 1991; 261(Heart Circ Physiology 30):H70-H76.

8. Igarashi Y, Cheng CP, Little WC. Left ventricular ejection activation in the in situ heart. Am J Physiology 1991; 260 (Heart Circ Physiology 29):H1495-1500.

9. Cheng CP, Igarashi Y, Little WC. Effect of felodipine on left ventricular performance in conscious dogs: assessment by left ventricular pressure-volume analysis. J Pharma & Exper Thera 1991; 257:163-169.

10. Cheng CP, Igarashi Y, Little WC. Mechanism of augmented rate of left ventricle filling during exercise. Circ Res 1992; 70:9-19.

11. Cheng, CP, Igarashi Y, Klopfenstein HS, Applegate RJ, Shihabi Z, Little WC. Effect of vasopressin on left ventricular performance. Am J. Physiol 1993; 264(1 Pt 2):H53-60.

12. Cheng CP, Noda T, Nozawa T, Little WC. Effect of heart failure on the mechanism of exercise induced augmentation of mitral valve flow. Circ. Res, 1993; 72:795-806.

13. Noda T, Cheng CP, de Tombe PP, Little WC. Curvilinearity of left ventricular end-systolic pressure-volume relation and dP/dtmax-end diastolic volume relations. Am J Physiol 1993; 265 (Heart Circ Physiol 34):H910-H917.

14. Nakamoto T, Cheng CP, Santamore WP, Iizuka M. Estimation of left ventricular elastance without altering preload or afterload in the conscious dog. Cardiovascular Res 1993; 27:868-873.

15. Little WC and Cheng CP. Effect of exercise on left ventricular-arterial coupling assessed in the pressure-volume plane. Am J Physiol 1993; 264 (Heart Circ Physiol 33) H1629-1633.

16. Cheng CP, Noda T, Nordlander M., Little WC. Comparison of effects of Dihydropyridine calcium antagonists on left ventricular systolic and diastolic performance. J Pharma & Exper Thera 1994; 268(3):1232-1241.

17. Little WC, Cheng CP. Coupling of the left ventricular and arterial system. Med & Biol Eng & Computer 1994; 32:205-209.

18. Nozawa T, Cheng CP, Noda T, Ohno M, Little WC. The relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs. Circulation 1994; 89:810-817.

19. Little WC, Cheng CP. Vascular versus myocardial effects of calcium antagonists. Drug 1994; 47(4):41-46.

20. Ohno M, Cheng CP, Little WC. Mechanism of Altered Patterns of left ventricular filling during the development of congestive heart failure. Circulation1994; 89:2241-2250.

21. Nozawa T, Cheng CP, Noda T, Little WC. Effect of exercise on left ventricular mechanical efficiency in conscious dogs. Circulation 1994; 90:3047-3054.

22. Cheng, CP, Pettersson K, Little WC. Effects of felodipine on left ventricular systolic and diastolic performance in congestive heart failure. J Pharma and Exper Thera 1994; 271:1409-1417.

23. Little WC, Ohno M, Kitzman DW, Thomas JD, Cheng CP. Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling. Circulation 1995; 92(7):1933-1939.

24. Little WC, Cheng CP, Elvelin L, Nordlander M. Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: Focus on felodipine. Cardiovasc Drugs Ther 1995; 9(5):657-663.

25. Kerkhof PLM., Weber MF, Vanoverschelde J-LJ, Cheng CP. Neural modulation of myocardial oxygen consumption, ventriculo-aortic coupling index and stroke work based on the alternative Starling curve. IEEE, 1995.

26. Cheng CP, Suzuki M, Ohte N, Ohno M, Wang Z.M., Little WC. Altered ventricular and myocyte response to angiotensin II in pacing-induced heart failure. Circ Res 1996; 78 :( 5)880-892.

27. Ohte N, Cheng CP, Suzuki, M, Little WC. The cardiac effects of pimobendan (but not amrinone) are preserved at rest and during exercise in conscious dogs with pacing-induced heart failure. J Pharma and Exper Thera 1997:282(1): 23-31.

28. Suzuki M, Cheng CP, Ohte N, Little WC. Left ventricular spherical dilation and regional contractile dysfunction in dogs with heart failure. American Journal of Physiology 1997:273:H1058-H1067.

29. MacRae JM, Sun Y-H, Isaac DL, Dobson GM, Cheng CP, Little WC, Parker KH, Tyberg JV. Wave-intensity analysis: a new approach to left ventricular filling dynamics. Heart and Vessels 1997; 12:53-59.

30. Little WC, Warner JG, Rankin KM, Kitzman DW, Cheng CP. Evaluation of left ventricular diastolic function from the pattern of left ventricular filling. Clinical Cardiology 1998; 21:5-9.

31. Cheng CP, Onishi K, Ohte N, Suzuki M, Little WC. Functional effects of endogenous bradykinin in congestive heart failure. JACC 1998; 31(7):1679-1686.

32. Little WC, Cheng CP. Diastolic Dysfunction. Cardiology in Review 1998; 6:231-239.

33. Suzuki M, Ohte N, Wang ZM, Williams DL, Jr., Little WC, Cheng CP. Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy. Cardiovascular Research 1998; 39:589-599.

34. Onishi K, Ohno M, Little WC, Cheng CP. Endogenous endothelin-1 depresses left ventricular systolic and diastolic performance in congestive heart failure. J Pharm Expe Therap 1999:288(3):1214-1222.

35. Ohte N, Cheng CP, Suzuki M, Little WC. Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure. J Pharm Expe Therap (JPET) 1999; 291:589-595.

36. Little WC, Cheng CP. Left atrial role in left ventricular filling at rest during exercise and during the development of heart failure. Eur Heart J 2000; 2(Suppl K): K17-K25.

37. Little WC, Kitzman DW, Cheng CP. Diastolic dysfunction as a cause of exercise intolerance. Heart Failure Reviews 2000; 5:301-306.

38. Ukai T, Cheng CP, Tachibana H, Igawa A, Zhang ZS, Cheng HJ, Little WC. Allopurinol enhances the contractile response to dobutamine and exercise in dogs with pacing-induced heart failure. Circulation 2001; 103:750-755.

39. Cheng CP, Ukai T, Onishi K, Ohte N, Suzuki M, Zhang ZS, Cheng HJ, Tachibana H, Igawa A, Little WC. The role of angiotensin II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure. Am J Physiol 2001; 280:H1853-H1860.

40. Zhang ZS, Cheng HJ, Ukai T, Tachibana H, Cheng CP. Enhanced cardiac L-type calcium current response to ÃŸ2-adrenergic stimulation in heart failure. J Pharm Expe Therap 2001; 298:188-196.

41. Shihabi ZK, Hinsdale ME, Cheng CP. Analysis of glutathione by capillary electrophoresis based on sample stacking. Electrophoresis 2001; 21:835-841.

42. Cheng HJ, Zhang ZS, Onishi K, Ukai T, Sane DC, Cheng CP. Upregulation of functional ÃŸ3-adrenergic receptors in the failing canine myocardium. Circulation Res 2001; 89:599-606.

43. Hasegawa H, Little WC, Ohno M, Brucks S, Morimoto A, Cheng HJ, Cheng CP. Diastolic mitral annular velocity during the development of heart failure. J Am Coll Cardiol 2003; 41:1590-1597.

44. Ohte N, Cheng CP, Little WC. Tachycardia exacerbates abnormal left ventricular-arterial coupling in heart failure. Heart & Vessels 2003; 18:136-141.

45. Little WC, Wesley-Farrington DJ, Hoyle J, Brucks S, Robertson S, Kitzman DW, Cheng CP. Effect of candesartan and verapamil on exercise tolerance in diastolic dysfunction. J Cardiovasc Pharmacol 2004; 43:288-293.

46. Morimoto A, Hasegawa H, Cheng HJ, Little WC, Cheng CP. Endogenous Î²3-adrenoreceptor activation contributes to left ventricular and cardiomyocyte dysfunction in heart failure. Am J Physiol 2004; 286:H2425-H2433.

47. Morimoto A, Hasegawa H, Cheng HJ, Little WC, Cheng CP. Endogenous Î²3-adrenoreceptor activation contributes to left ventricular and cardiomyocyte dysfunction in heart failure. Lead Discovery, Daily Updates Alert, Feb. 23, 2004.

48. Tachibana H, Cheng HJ, Ukai T, Igawa A, Zhang ZS, Little WC, Cheng CP. Levosimendan improves left ventricular systolic and diastolic performance at rest and during exercise after heart failure. Am J Physiol Heart Circ Physiol 2004; 288:H914-H922.

49. Zhang ZS, Cheng HJ, Onishi K, Ohte N, Wannenburg T, Cheng CP. Enhanced inhibition of L-type Ca2+ current by beta3-adrenergic stimulation in failing rat heart. J Pharm Expe Therap 2005; 315: 1203-1211.

50. Cheng CP, Cheng HJ, Cunningham C, Shihabi ZK, Sane DC, Wannenburg T, Little WC. Angiotensin II type 1 receptor blockade prevents alcoholic cardiomyopathy. Circulation 2006; 114:226-236.

51. Cheng HJ, Han QH, Masutani S, Grant KA, Daunais JB, Friedman DP, WC Little WC, Cheng CP. Functional significance of cardiac beta3-adrenoreceptors in alcoholic monkeys. ABMRF Conference Proceedings from the IMAG Meeting, 2006.

52. Cheng CP, Masutani S, Cheng HJ, Cross M1, Hyttila-Hopponen M, Levijoki J, Heikkila A, Vuorela A, Little WC. Oral Levosimendan enhances left ventricle systolic and diastolic performance prior to and after pacing-induced heart failure in dogs. Conference Proceedings from the ACVIM (American College of Veterinary Internal Medicine) Meeting, 2007.

53. Masutani S, Little WC, Hasegawa H, Cheng HJ, Cheng CP. Restrictive left ventricular filling pattern does not result from increased left atrial pressure alone. Circulation 2008; 117:1550-1554.

54. Masutani S, Cheng HJ, HyttilÃ¤-Hopponen M, Levijoki J, HeikkilÃ¤ A, Vuorela A, Little WC, Cheng CP. Orally available levosimendan dose-related positive inotropic and lusitropic effect in conscious chronically instrumented normal and heart failure dogs. J Pharmacol Exp Ther 2008; 325:236-247.

55. Masutani S, Little WC, Hasegawa H, Cheng HJ, Cheng CP. Response to letter regarding article, â€œrestrictive left ventricular filling pattern does not result from increased left atrial pressure aloneâ€. Circulation 2008; 118: e506.

56. Frankel AE, Kuo SR, Dostal D, Watson L, Duesbery NS, Cheng CP, Cheng HJ, Leppla SH. Pathophysiology of anthrax. Front Biosci 2009; 14:4516-4524.

57. Cheng HJ, Grant KA, Han QH, Daunais JB, Friedman DP, Masutani S, Little WC, Cheng CP. Up-regulation and functional effect of cardiac ?3-adrenoreceptors in alcoholic monkeys. Alcohol Clin Exp Res 2010; 34:1-11.

58. Masutani S, Cheng HJ, Tachibana H, Little WC, Cheng CP. Levosimendan restores the positive force-frequency relation in heart failure. Am J Physiol Heart Circ Physiol 2011; 301:H488-H496.

59. Masutani S, Cheng HJ, Han QH, Little WC. Cheng CP. Beta3-adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure. Am J Physiol Heart Circ Physiol 2013; 305:H923-H930.

60. Liu YX, Geng JQ, Liu YT, LiY, Shen JX, Xiao XP, Sheng L, Cheng CP, Li WM. Î²3-Adrenoceptor Mediates Metabolic Protein Remodeling in a Rabbit Model of Tachypacing-Induced Atrial Fibrillation. Cell Physiol Biochem 2013; 32:1631-1642.

61. Upadhya B, Taffet GE, Cheng CP, Kitzman DW. Heart failure with preserved ejection fraction in the elderly: scope of the problem. Journal of Molecular and Cellular Cardiology 83 (2015) 73â€“87.

62. Zhou P, Cheng CP, Li TK, Ferrario CM, Cheng HJ. Modulation of cardiac L-type Ca2+ current by angiotensin-(1-7): normal vs heart failure. Therapeutic Advances in Cardiovascular Disease 2015, December; 9(6): 342â€“353. doi:10.1177/1753944715587424.

63. Dong JM, Zhao JJ, Zhang MM, Liu GZ, Wang XB, Liu YX, Yang N, Liu YW, Zhao GQ, Sun JY, Tian JP, Li Y, Cheng CP, Li WM. Î²3-adrenoceptor Impairs Mitochondrial Biogenesis and Energy Metabolism During Rapid Atrial Pacing-induced Atrial Fibrillation. Journal of Cardiovascular Pharmacology and Therapeutics 2015; June 30, 1-13. PMID: 26130614

64. Shao Q, Cheng HJ, Callahan MF, Kitzman DL, Li WM, Cheng CP. Overexpression Myocardial Inducible Nitric Oxide Synthase Exacerbates Cardiac Dysfunction and Beta-Adrenergic Desensitization in Experimental Hypothyroidism. International Journal of Cardiology 204 (2016) 229-241.

65. Li TK, Cheng HJ, Ohte N, Hasegawa H, Morimoto A, Little WC, Cheng CP. C-Type Natriuretic Peptide Improves Left Ventricular Functional Performance at Rest and Restores Normal Exercise Responses after Heart Failure. J Pharmacol Exp Ther 357:545â€“553, June 2016 DOI: 10.1124/jpet.115.231696. PMC 4885509.

66. Allan K. Alencar, Jaqueline S. da Silva, Marina Lin, Ananssa M. Silva, Xuming Sun, Carlos M. Ferrario, Cheping Cheng, Roberto T. Sudo, Gisele Zapata-Sudo, Hao Wang, Leanne Groban. Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344xBrown Norway Female Rat. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2016; doi: 10.1093/gerona/glw045. PMC 15008653.

67. Carlos M Ferrario, Sarfaraz Ahmad, Jasmina Varagic, Che Ping Cheng, Leanne Groban, Hao Wang, James Collawn, Louis J Dellâ€™Italia. Intracrine Angiotensin II Functions Originate from Non-Canonical Pathways in the Human Heart. Am J Physiol Heart Circ Physiol (May 27, 2016). doi:10.1152/ajpheart.00219.2016.

68. Santiago Reyes, Sarfaraz Ahmad, Jessica VonCannon, Neal D. Kon, Hao Wang, Leanne Groban, Che Ping Cheng, Jasmina Varagic, Joseph L. Dellâ€™Italia, Carlos M. Ferrario. Novel Cardiac Intracrine Mechanisms Based on Ang-(1-12)/Chymase Axis in Human Heart Disease Require a Revision of Therapeutic Approaches. Curr Hypertens Rep (2017) 19:16 DOI 10.1007/s11906-017-0708-3.

69. Zhang XW, Cheng HJ, Zhou P, Kitzman DW, Ferrario CM. Li WM, Cheng CP. Cellular basis of angiotensin-(1-7)-induced augmentation of left ventricular functional performance in heart failure. International Journal of Cardiology 236 (2017) 405â€“412 http://dx.doi.org/10.1016/j.ijcard.2017.01.071.

70. Tiankai Li, Xiaowei Zhang, Sarfaraz Ahmad, Jasmina Varagic, Heng-Jie Cheng, Carlos M. Ferrario, Che Ping Cheng. Direct Cardiac Functional Responses to Chymase/Ang-(1-12) Pathway Activation in Normal and Heart Failure Cardiomyocytes. Hypertension 2017 (in revision).

71. Hasegawa H, Morimoto A, Cheng HJ, Igawa A, Little WC, Cheng CP. Omapatrilat improves arterial coupling and mechanical efficiency and restores normal exercise response in heart failure. Am J Physiol 2017 (in revision).

72. Zhang XW, Li TK, Cheng HJ, Wang H, Li WM, Ferrario CM, Leanne Groban L, Cheng CP. Chronic GPER Activation Attenuates Cardiac Dysfunction in a Male Mouse Model of Progressive Heart Failure: Insights into Cellular Mechanisms. International Journal of Cardiology 2017 (in revision).

Book Chapters

1. Cheng CP, Shihabi A, Little WC. Mildly intoxicating levels of alcohol produces direct myocardial depression on left ventricular performance. In: Novel Pharmacological Interventions for Alcoholism. Springer-Verlag New York Publishers, NY, 1992, 278-287.

2. Little WC, Cheng CP. Effect of felodipine on left ventricular performance in conscious dogs: Assessment by left ventricular pressure-volume analysis. In: Calcium Antagonists: Pharmacology and Clinical Research. Eds., Godfraind T, Govoni S, Paoletti R, Vanhoutte PM. Kluwer Academic Publishers, The Netherlands, 1993.

3. Little WC, Cheng CP. Modulation of diastolic dysfunction in the intact heart. In: Diastolic Relaxation of the Heart. Ed., B.H. Lorell and W. Grossman, Kluwer Academic Publishers, Boston, MA, 1994, 167-176.

4. Little WC, Cheng CP. Left ventricular systolic and diastolic performance. Ed., D.C. Warltier. In: Ventricular Function, Williams & Wilkins, Baltimore, 1995:111-129.

5. Little WC, Cheng CP. Response of left ventricular filling to exercise before and after heart failure. Ed., N.B. Ingels, Jr., G.T. Daughters, J. Baan, J.W. Covell, R.S. Reneman, F.C-P Yin. In: Systolic and Diastolic Function of the Heart. IOS Press and Ohmsha, The Netherlands. 1996, 157-166.