Abstract：
:In general, plasma concentrations of high density lipoproteins (HDL) are inversely related to the incidence of coronary artery disease. One exception to this trend is individuals with apolipoprotein A-I(Milano) (apo A-IM), a molecular variant of apo A-I, which results in very low plasma apo A-I and HDL-cholesterol levels. Despite these low levels, and other lipoprotein defects, individuals with this mutation have no increased risk for cardiovascular disease. As a first step in proving why apo A-IM carriers appear to be protected from the pro-atherogenic effect of a low HDL, transgenic mice expressing apo A-IM were generated. Mice expressing either wild-type human apo A-I or apo A-IM, together with human apo A-II, were crossed into mice lacking murine apo A-I. Apo A-IM/A-II mice had lower cholesterol and HDL plasma levels compared to apo A-I/A-II mice. Moreover, as in human carriers, apo A-IM mice were characterized by elevated triglyceride plasma levels and by the presence of a population of very small HDL particles. These results indicate that the expression of apo A-IM in a mouse model reproduces the major lipid/lipoprotein abnormalities observed in human carriers. Thus, apo A-IM transgenic mice appear to be a suitable model in which to assess whether the mutation has an anti-atherogenic effect.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Chiesa G,Stoltzfus LJ,Michelagnoli S,Bielicki JK,Santi M,Forte TM,Sirtori CR,Franceschini G,Rubin EMdoi
10.1016/s0021-9150(97)00195-0subject
Has Abstractpub_date
1998-01-01 00:00:00pages
139-46issue
1eissn
0021-9150issn
1879-1484pii
S0021-9150(97)00195-0journal_volume
136pub_type
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