Physiology

MING GONG, Ph.D. Associate Professor Ph.D. Peking Union Medical College, China, 1994 Office: CTW-509, Health Sciences Building 0200 Tel: (859) 323-4933 ext. 81361 Fax: (859) 257-3646 Lab: CTW-511, Tel: 323-4933 ext. 81372 E-mail: ming.gong@uky.edu Curriculum Vita (pdf)

Current research in our laboratory focuses on vascular mechanisms of type 2 diabetes associated hypertension and blood pressure circadian rhythm disruptions

More than 170 million people worldwide have diabetes. Hypertension occurs more frequently in these diabetic patients than in those without diabetes. Moreover, when hypertension is superimposed on diabetes, the progression of diabetic complications becomes significantly more severe. However, the mechanisms by which diabetes cause an increase in the incidence of hypertension are not well understood. We and others have found that type 2 diabetic mouse models, db/db mice and high fat-diet fed mice, are hypertensive and vascular smooth muscle tissues isolated from them manifest contractile hyper-reactivity. One of our goals is to elucidate the molecular mechanisms underlying such vascular smooth muscle hyper-reactivity and its role in diabetes associated hypertension. Currently, we are focusing on the role of CPI-17, a myosin phosphatase inhibitory protein that is preferentially expressed in smooth muscle and plays an important role in regulating physiological smooth muscle contraction. We found that CPI-17 is activated and up-regulated in vascular smooth muscle of type 2 diabetic mice.

Blood pressure has a circadian pattern characterized by a low period during sleep; an early morning, post awakening rise; and a high plateau period while the subject is awake. There is increasing evidence that not only does the average level of blood pressure, but particularly an abnormal circadian blood pressure rhythm with a decreased fall in night time blood pressure, determine the development of diabetic complications and cardiovascular outcomes. The mechanisms that account for the abnormal blood pressure diurnal pattern in type 2 diabetes remain largely unknown. We are currently exploring the role of dysregualted core clock genes and vascular smooth muscle contractile diurnal variations in diabetes associated blood pressure circadian rhythm disruptions.

Combinations of the state-of-the-art techniques with classical physiological and biochemical methods were used to pursue our goals. These include radiotelemetry monitoring mouse blood pressure, smooth muscle specific transgenic and knockout mouse models, isometric contraction determination with isolated vascular tissues, microarray, real-time PCR, small interference RNA and adenoviral mediated gene transfer.

Recent publications:

Huan Pang, Zhenheng Guo, Wen Su, Masumi Eto and Ming C. Gong (2005). RhoA/rho kinase mediates thrombin- and U-46619-induced phosphorylation of a myosin phosphatase inhibitor, CPI-17, in vascular smooth muscle cells. American Journal of Physiology (Cell), 289: C352-C360

Zhenheng Guo, Wen Su, Shannon Allen, Huan Pang, Alan Daugherty, Eric Smart and Ming C. Gong (2005). COX-2 Up-regulation and vascular smooth muscle contractile hyperreactivity in spontaneous diabetic db/db mice. Cardiovascular Research 67: 723-735.

Zhongwen Xie, Wen Su, Zhenheng Guo, Huan Pang, Steven Post and Ming C. Gong (2006): Up-regulation of CPI-17 Phosphorylation in Diabetic Vasculature and High Glucose Cultured Vascular Smooth Muscle Cells. Cardiovascular Research, 69: 491-501

Karyn A. Esser, Wen Su, Sergey Matveev, Vicki Wong, Li Zeng, John J. McCarthy, Eric J. Smart, Zhenheng Guo, and Ming C. Gong (2007): Voluntary Wheel Running Ameliorates Vascular Smooth Muscle Hyper-contractility in Type 2 Diabetic db/db Mice. Applied Physiology, Nutrition and Metabolism 32(4): 711-20

Wen Su, Zhenheng Guo, David C. Randall, Lisa A. Cassis, David R. Brown, Ming C. Gong (2008) Hypertension and Disrupted Blood Pressure Circadian Rhythm in Type 2 Diabetic db/db Mice. American Journal of Physiology-Heart and Circulation, 295: H1634-H1641

Other Publications