Enhanced atherothrombotic formation after oxidative injury by FeCl3 to the common carotid artery in severe combined hyperlipidemic mice.

Abstract

UNLABELLED:

Enhanced susceptibility to atherosclerosis from severe hypertriglyceridemia (HTG) resulting from lipoprotein lipase (LPL) deficiency has been demonstrated in our recent findings which employed a unique mouse model. In the present study we provide further evidence that severe HTG due to LPL deficiency also promotes an atherothrombotic response to arterial injury induced by ferric chloride in a severe combined hyperlipidemic mouse model.

METHODS AND RESULTS:

A mouse model (LPL(-/-)XApoE(-/-) double knockout, DKO) with severe combined hyperlipidemia was established by crossing ApoE and LPL-deficient mice. The common carotid arteries of ApoE knockout (EKO) and DKO mice were subjected to injury by ferric chloride, and the formation of arterial thrombosis together with various markers were compared in these lesions. DKO mice demonstrated significantly enhanced thrombus formation overlying atherosclerotic plaque after injury, which contained smooth muscle cells, macrophages, and neutral lipid. The area of neointima, mean intima/media ratios, and the percentage of luminal stenosis were significantly greater (P<0.01) in DKO mice. Compared with EKO mice, the expression of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1) were increased in DKO mice.

CONCLUSIONS:

Severe combined hyperlipidemia promotes thrombosis after ferric chloride injury to atherosclerotic vessels and HTG plays a major role in the process.

• Authors: Xunde Xian, Yu Ding, Ling Zhang, Yanan Wang, Michael A McNutt, Colin Ross, Michael R Hayden, Xuming Deng, George Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 385 Issue 4 Pg. 563-9 (Aug 07 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19481534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Chlorides
• Ferric Compounds
• Plasminogen Activator Inhibitor 1
• von Willebrand Factor
• Lipoprotein Lipase

Topics

• Animals
• Apolipoproteins E (genetics)
• Atherosclerosis (chemically induced, etiology, pathology)
• Carotid Artery, Common (drug effects, pathology)
• Chlorides (toxicity)
• Disease Models, Animal
• Ferric Compounds (toxicity)
• Hypertriglyceridemia (complications, genetics)
• Lipoprotein Lipase (genetics)
• Mice
• Mice, Knockout
• Oxidative Stress
• Plasminogen Activator Inhibitor 1 (biosynthesis)
• Thrombosis (chemically induced, etiology, pathology)
• von Willebrand Factor (biosynthesis)