中國醫藥大學競爭性團隊研究中心計畫
中文計畫名稱: L5醫學研究中心
英文計畫名稱: L5 Medical Research Center
主持人
單位
職稱
總計畫
李源德
醫學系
講座教授
子計畫1
馬明琪
分統所
教授
子計畫2
汪貴珍
國立中國醫藥研究所
教授
子計畫3
張坤正
醫學系
副教授
子計畫4
施庭芳
台大附設醫院
放射科
教授
子計畫5
張永賢
針灸所
教授
整合型總計畫名稱：
Identification of a Novel
Cardiovascular Risk Factor through
a Translational Approach
• Director: 李源德 講座教授
• Co-Director: Chu-Huang Chen (陳珠璜), MD PhD,
Associate Professor, Baylor College of Medicine
The composition of a new cardiovascular
research center at CMU-CMUH:
L5 Medical Research Center
What is L5?
Electronegative LDL mildly oxidized in vivo.
L5 is the most highly electronegative LDL.
L5 can induce apoptosis of vascular endothelial cells.
Endothelial apoptosis contributes to atherosclerosis and
thrombosis.
LDL-C = 190 mg/dl
LDL-C = 119 mg/dl
L5 composition and its distinction
from HDL
Tang et al. ACC meeting in
Chicago, April 1st 2008
Who has L5?
Metabolic Syndrome
LDL-C all ranges
Hypercholesterolemia
LDL-C >160 mg/dL
L5
Type 2 DM
LDL-C all ranges
Chronic Smokers
LDL-C all ranges
Interruption of the FGF2-PI3K-Akt
Autoregulatory Loop by L5
Lu and Jiang et al. Diabetes 2008
Internalization of L5 and oxLDL by
LOX-1 and endocytosis of L1 by LDLR
Role of LOX-1 in smoker L5 induced
mitochondrial disruption
Tang et al. ACC meeting in Chicago. April 1st 2008
Chen’s lab
Effect of Zetia on L5 reduction in
hamster fed with high-fat diet
L5 UnoQ6 B 10ml HF001:10_UV
L5 UnoQ6 B 10ml HF001:10_Fractions
L5 UnoQ6 B 10ml control001:10_UV
L5 UnoQ6 B 10ml Zetia001:10_UV
mAU
L1 (%)
83.36
57.74
93.31
Control (normal diet)
HFHC diet
HFHC diet + ezetimibe
80
L5 (%)
16.64
42.26
6.69
Control (normal diet)
60
HFHC diet
HFHC diet + ezetimibe
40
20
0
1 2 3 4 5 6 7 8 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65 67 69 71 73
0
20
40
60
80
100
120
140
75
min
Morphological changes in EPC colonies
with sustained exposure to L5 vs. L1
Goal and significance
of the new cardiovascular research center
• Goal
– to establish an in vivo relevance of L5 in
atherosclerosis.
• Significance
– Impact on public health in Taiwan
– Impact on medical research in Taiwan
Missions of the core laboratory and
all divisions
• Core Laboratory: (陳珠璜Assoc. Prof; 楊朝諭教授) 黃志
揚教授 汪貴珍教授 張博淵助理教授 李安生助理教授
– will be providing L5 for cell and animal studies and
performing all L5 analyses
– fully characterize L5 and strengthen the theoretical
basis for all the studies
• Division I—Cell Study Division (馬明琪教授; 李啟明副教授)
黃志揚教授, 李宗貴教授, 陳珠璜Assoc. Prof
– to provide further evidence of L5’s capability of deranging
the molecular homeostasis.
– strengthen the theoretical basis for the animal and human
studies
– provide insights into new targets for treatment
• 子計畫:
– Effects of L5 on macrophage physiology
– Effects of L5 on endothelium-dependent vascular functions
– Effects of L5 on the expression of adhesion molecules in
endothelial cells
– Effects of L5 on hypertrophy and apoptosis in
cardiomyocytes
• Division II—Animal Study Division: (汪貴珍教授, 郭薇雯副
教授), 李安生助理教授, 陳珠璜Assoc. Prof
– will be performing animal studies to establish the in vivo
relevance of L5 in atherosclerosis.
– to provide sufficient evidence to establish such a causeeffect relation.
• 子計畫:
– Induction of L5 synthesis in hamsters and investigation of
the mechanism
– Effects of L5 on EDR in aortic ring preparations
– Role of L5 in diabetic cardiomyopathy in rat models
• Division III—Clinical Study Division: (張坤正副教授, 張博淵助
理教授), 白培英醫師, 張詩聖醫師, 李源德講座教授, 陳珠璜
Assoc. Prof
– To establish clinical correlation between L5 and
atherosclerosis
– To provide human plasma samples for L5 isolation and
purification at the core laboratory.
• 子計畫:
– L5 as a possible risk factor in CAD events
• To test relationship of L5 with progress of
atherosclerosis
• To identify the specific modified lipids and/or proteins
/peptides in L5
• To link to Pilot Clinical Trials with statin and Red rice
• Division IV—Imaging Study Division: (施庭芳教授, 何永仁主
任), 沈戊忠教授, 李源德講座教授, 張坤正副教授, 陳珠璜
Assoc. Prof
– to provide direct visual evidence of vascular disease in
humans
– to establish a close correlation between L5 concentration
and tissue perfusion in humans by using DCE-MRI
technology
• 子計畫:
– Correlation between plasma L5 levels and pancreatic
perfusion in humans
• Division V—Pilot Trial Study Division: (張永賢副校長, 陳清
助主任), 汪貴珍教授, 郭薇雯副教授, 王宇澄醫師, 陳珠璜
Assoc. Prof
– to identify natural products as alternative regiments for L5
reduction in high risk patients, and
– to examine whether L5 reduction is accompanied by
clinical improvement of endothelial function. The two
products to be tested are Monascus purpureus (紅麴) and
garlic extract (大蒜).
• 子計畫:
– Effect of Monascus purpureus on L5 reduction in patients
with T2DM
– Effect of garlic on L5 reduction in patients with T2DM
THANK YOU FOR YOUR ATTENTION!