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Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice.

Abstract：

OBJECTIVE:Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism and atherosclerosis in uremic apoE-/- mice. METHODS AND RESULTS:Upon intraperitoneal injection, h-apoA-I and TripA-I rapidly associated with plasma HDL and reduced mouse apoA-I plasma levels without affecting total or HDL cholesterol concentrations. The plasma half-life was approximately 36 h for TripA-I and approximately 16 h for h-apoA-I. Injection of h-apoA-I (100mg/kg) or TripA-I (100mg/kg) twice weekly for 7 weeks did not affect the cross-sectional area of atherosclerotic lesions in the aortic root, or the en face lesion area and cholesterol content in the thoracic aorta in uremic apoE-/- mice. Also, the treatments did not affect expression of selected inflammatory genes in the thoracic aorta or plasma concentrations of soluble ICAM-1 and VCAM-1. However, h-apoA-I-treated mice had larger smooth muscle cell-staining areas in aortic root plaques than PBS-treated mice (4.8+/-0.8% vs. 2.5+/-0.6%, P<0.05). CONCLUSIONS:The data suggest that long-term treatment with non-lipidated h-apoA-I or TripA-I might affect plaque composition but does not reduce atherosclerotic lesion size in uremic apoE-/- mice.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Pedersen TX,Bro S,Andersen MH,Etzerodt M,Jauhiainen M,Moestrup S,Nielsen LB

doi

10.1016/j.atherosclerosis.2008.04.041

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

372-81

issue

2

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(08)00279-7

journal_volume

202

pub_type

杂志文章

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