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Overexpression of human apolipoprotein A-I in transgenic rats and the hyperlipoproteinemia associated with experimental nephrosis.

Abstract：

:Hyperlipoproteinemia contributes both to kidney disease progression and the development of atherosclerosis. Elevated high density lipoprotein cholesterol and apolipoprotein A-I (apoA-I) serum levels are independent factors protective against the atherosclerotic process. We examined the effects in a transgenic rat model of human apoA-I expression on the hyperlipoproteinemia and edema after puromycin aminonucleoside-induced nephrosis in three groups of animals: low line (TgR[hAI]low, human plasma apoA-I = 16.0 mg/dl); high line (TgR[hAI]high, 284 mg/dl); and non-transgenic litter mates (TgR[hAI]non). Nephrosis increased total plasma apoA-I levels 2-fold in TgR[hAI]non rats (75 vs. 162 mg/dl) and 4-fold in the TgR[hAI]low (97 vs. 458 mg/dl) and TgR[hAI]high rats (356 vs. 1,346 mg/dl). In both transgenic lines, this increase was due mainly to elevations of serum human apoA-I. The hepatic steady-state levels of rat apoA-I mRNA increased 5- to 7-fold in all three groups, while human apoA-I mRNA levels increased 21- and 65-fold in the low and high expressing groups, respectively, indicating a different degree of responsiveness of the rat and human genes. While nephrotic TgR[hAI]non and TgR[hAI]low rats showed severe hyperlipoproteinemia and edema, much lower levels of edema and of serum triglycerides, phospholipids, and cholesterol were seen in the TgR[hAI]high group. Urinary excretion of apoA-I, phospholipids, and cholesterol was significantly increased in the TgR[hAI]high group, indicating this as one possible mechanism for the relatively lower serum levels of these lipids. We conclude that the human apoA-I gene is responsive to nephrosis and that human apoA-I-transgenic rats with this syndrome provide an animal model for the study of human high density lipoprotein and apoA-I metabolism.

journal_name

J Lipid Res

journal_title

Journal of lipid research

authors

Burkey BF,France D,Wang H,Ma X,Brand B,Abuhani C,Diffenderfer MR,Marsh JB,Paterniti JR Jr,Fisher EA

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

1463-73

issue

eissn

0022-2275

issn

1539-7262

journal_volume

pub_type

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Overexpression of human apolipoprotein A-I in transgenic rats and the hyperlipoproteinemia associated with experimental nephrosis.