This Article Full Text Full Text (PDF) All Versions of this Article: 25/9/e128    most recent 01.ATV.0000175760.28378.80v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rotllan, N. Articles by Escolà-Gil, J. C. Search for Related Content PubMed PubMed Citation Articles by Rotllan, N. Articles by Escolà-Gil, J. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL TRITIUM

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:e128.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Overexpression of Human Apolipoprotein A-II in Transgenic Mice Does Not Impair Macrophage-Specific Reverse Cholesterol Transport In Vivo

Noemí Rotllan; Vicent Ribas; Laura Calpe-Berdiel; Jesús M. Martín-Campos; Francisco Blanco-Vaca; Joan Carles Escolà-Gil

From Servei de Bioquímica and Institut de Recerca (N.R., V.R., L.C-B., J.M. M-C, F.B-V., J.C.E-G.), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

Correspondence to Joan Carles Escolà-Gil or Francisco Blanco-Vaca, Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Antoni M Claret 167, 08025 Barcelona, Spain. E-mail jescola{at}hsp.santpau.es or fblancova@hsp.santpau.es

Background— Overexpression of human apolipoprotein (apo) A-II in transgenic mice induces high-density lipoprotein (HDL) deficiency, and increased atherosclerosis susceptibility only when fed an atherogenic diet. This may, in part, be caused by impairment in reverse cholesterol transport (RCT).

Methods and Results— [³H]cholesterol-labeled macrophages were injected intraperitoneally into mice maintained on a chow diet or an atherogenic diet. Plasma [³H]cholesterol did not differ from human apoA-II transgenic and control mice at 24 or 48 hours after the label injection. On the chow diet, human apoA-II transgenic mice presented increased [³H]cholesterol in liver (1.3-fold) and feces (6-fold) compared with control mice (P<0.05). The magnitude of macrophage-specific RCT did not differ between transgenic and control mice fed the atherogenic diet.

Conclusions— Human apoA-II maintains effective RCT from macrophages to feces in vivo despite an HDL deficiency. These findings suggest that the increased atherosclerotic lesions observed in apoA-II transgenic mice fed an atherogenic diet are not caused by impairment in macrophage-specific RCT.

Macrophage-specific reverse cholesterol transport was measured in human apoA-II transgenic mice. Increased fecal [³H]cholesterol excretion was found in chow-fed transgenic mice, a situation in which there is no increased atherosclerosis. No significant differences were observed in atherogenic-fed mice, a situation in which there is a marked increase in atherosclerosis.

Key Words: apolipoprotein A-II • atherosclerosis • high-density lipoprotein • macrophages • reverse cholesterol transport