Lipoprotein Lipase (LPL) Deficiency Increases Plasma Lipid Level and Enhances Neointima Formation After Carotid Artery Injury in apoE Knock-out Mice
冼勋德 刘国庆
北京大学心血管研究所
Candidate genes in lipoprotein metabolism
Lusis et al Circulation. 2004
Lipoprotein Lipase in the Arterial Wall
Pentik?inen et al Arterioscler Thromb Vasc Biol. 2002
Lipoprotein Lipase in the Arterial Wall
Pentik?inen et al Arterioscler Thromb Vasc Biol. 2002
Hypothesis
LPL
Arterial response to injury
hyperlipidemic conditions
？
A 1x2-mm strip of filter paper saturated with 10% FeCl3 solution was applied to the adventitial surface of the surgically exposed carotid artery for 3.0 minutes, then removed. The surgical incision was sutured with 4–0 monofilament, and the animal was returned to its cage.
Common carotid arteries of apoE-/-, LPL+/- (ELK)mice (A) and apoE-/-, LPL+/+ (EK)mice (B) 8 weeks after ferric chloride injury
neointima formation after carotid artery injury by FeCl3 for 8 weeks
ELK
carotid artery stained with H&E
EK
noninjured
injured
neointima formation after carotid artery injury by FeCl3 for 8 weeks
carotid artery stained with H&E
ELK
EK
noninjured
injured
Mean Intimal and Medial Cross-sectional Areas of EK and ELK Mice 8 Weeks after Injury
EK
ELK
**
*
lipid deposit after carotid artery injury by FeCl3 for 8 weeks
ELK
EK
control carotid artery stained with ORO
noninjured
injured
lipid deposit after carotid artery injury by FeCl3 for 8 weeks
ELK
EK
carotid artery stained with ORO
noninjured
injured
lipid deposit after carotid artery injury by FeCl3 for 8 weeks
ELK
EK
carotid artery counterstained with ORO and haematoxylin
injured
noninjured
lipid deposit after carotid artery injury by FeCl3 for 8 weeks
ELK
EK
carotid artery counterstained with ORO and haematoxylin
noninjured
injured
Macrophage stain for 8 weeks
ELK
EK
ELK
EK
Von Willebrand Factor Stain for 8 weeks
**
**
NS
NS
*
*
NS
NS
NS
EK
ELK
neointima formation after carotid artery
injury by FeCl3 for 4 weeks
carotid artery stained with H&E
lipid deposit after carotid artery
injury by FeCl3 for 4 weeks
ELK
EK
carotid artery counterstained with ORO and haematoxylin
Reference
Mary Beth DeYoung, Clifford Tom, David A. Dichek, et al Plasminogen Activator Inhibitor Type 1 Increases Neointima Formation in Balloon-Injured Rat Carotid Arteries. Circulation. 2001;104:1972-1977
Koichi Kaikita, Agnes B. Fogo, Lijun Ma, John A. Schoenhard, Nancy J. Brown, Douglas E. Vaughan, et al Plasminogen Activator Inhibitor-1 Deficiency Prevents Hypertension and Vascular Fibrosis in Response to Long-term Nitric Oxide Synthase Inhibition. Circulation. 2001;104:839-844
Yanhong Zhu, Peter M. Farrehi, William P. Fay, et al Plasminogen Activator Inhibitor Type 1 Enhances Neointima Formation After Oxidative Vascular Injury in Atherosclerosis-Prone Mice. Circulation. 2001;103:3105-3110
Marianne Pynn, Katrin Sch?fer, Stavros Konstantinides, Martin Halle, et al Exercise Training Reduces Neointimal Growth and Stabilizes Vascular Lesions Developing After Injury in Apolipoprotein E–Deficient Mice Circulation. 2004;109:386-392
Future Works
PAI-1↑
LPL↓
Neointima formation↑
？
？
Other Pathways
？
Thank You！