Even with substantial improvements in cardiovascular disease (CVD) treatments, CVD continues to be the leading cause of death in China. Epidemiologic studies and large-scale clinical trials have conclusively established a strong inverse relationship between high-density lipoprotein (HDL) cholesterol levels and cardiovascular risk. Insight into the dynamic differences in HDL biology and function in complication prone individual will identify new diagnostic markers and therapeutic targets in subjects with CVD. To gain this insight, we propose to develop state-of-the-art mass spectrometry based platform to identify and validate novel HDL protein markers that would predict risk of endothelial dysfunction in CVD patients. The proposed study will examine the roles and myeloperoxidase (MPO)-oxidized HDL and HDL proteome in vascular dysfunction in Chinese patients, comparing this data to data collected at UMHS. 

Numerous training opportunities were derived from the collaboration, including:

• 3 PKUHSC junior faculty members received extensive training at Michigan Medicine mentored by Dr. Eugene Chen and Dr. Sub Pennathur.
• 3 Michigan Medicine residents completed one-month clinical rotation at PKUHSC mentored by Dr. Wei Gao and Dr. Guisong Wang.

1. Wang G, Mathew AV, Yu H, Li L, He L, Gao W, Liu X, Guo Y, Byun J, Zhang J, Chen YE, Pennathur S. Myeloperoxidase Mediated HDL Oxidation and HDL Proteome Changes Do Not Contribute to Dysfunctional HDL in Chinese Subjects with Coronary Artery Disease. PLoS One. 2018,13 (3) :e0193782.
2. Liu D, Ji L, Tong X, Pan B, Han JY, Huang Y, Chen YE, Pennathur S, Zhang Y, Zheng L. (2011). Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through ATP-binding cassette transporter A1. American Journal of Cell Physiology. 2011;301(3): C739- 48. 
3. Pan B, Ma Y, Ren H, He Y, Wang Y, Lv X, Liu D, Ji L, Yu B, Wang Y, Chen YE, Pennathur S, Smith JD, Liu G, Zheng L. (2012) Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression. PLoS One. 2012; 7(11): e48530.
4. Guo Y, Fan Y, Zhang J, Lomberk GA, Zhou Z, Sun L, Mathison AJ, Garcia-Barrio MT, Zhang J, Zeng L, Li L, Pennathur S, Willer CJ, Rader DJ, Urrutia R, Chen YE. (2015) Perhexiline Activates KLF14 and Reduces Atherosclerosis by Modulating ApoA-I Production.  Journal of Clinical Investigation. 2015;125(10):3819-3830. doi:10.1172/JCI7904.
5. Pan B, Yu B, Ren H, Willard B, Pan L, Zu L, Shen X, Ma Y, Li X, Niu C, Kong J, Kang S, Eugene Chen Y, Pennathur S, Zheng L. (2013) High-density lipoprotein nitration and chlorination catalyzed by myeloperoxidase impair its effect of promoting endothelial repair. Free Radical Biology Medicine. 2013; 60: 272-81. 

NIH R01-HL134569 (Chen)                          

3/1/2017-2/28/2021                    

Title: KLF14 and Atherosclerosis

Total Funding: $2,821,885