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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1543.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Expression of Mouse Acute-Phase (SAA1.1) and Constitutive (SAA4) Serum Amyloid A Isotypes

Influence on Lipoprotein Profiles

Mark S. Kindy; Maria C. de Beer; Jin Yu; Frederick C. de Beer

From the Departments of Biochemistry (M.S.K., M.C.d.B., J.Y.), Surgery (M.S.K., J.Y.), and Internal Medicine (M.S.K., M.C.d.B., F.C.d.B.) and the Stroke Program of the Sanders-Brown Center on Aging (M.S.K., J.Y.), University of Kentucky School of Medicine, Lexington, and the Department of Veterans Affairs Medical Center (M.S.K., M.C.d.B., F.C.d.B.), Lexington, Ky.

Correspondence to Mark S. Kindy, PhD, Department of Biochemistry, University of Kentucky Medical Center, 800 Rose St, Lexington, KY 40536-0084. E-mail mskindy{at}pop.uky.edu

Abstract—The serum amyloid A (SAA) family of proteins consists of inducible acute-phase members and a constitutive member that are minor apolipoproteins of normal high density lipoprotein (HDL). During inflammation, HDL cholesterol and apolipoprotein A-I (apoA-I) protein are decreased, and these changes are thought to be partly related to the increase in acute-phase SAA proteins that associate with the HDL particle to become the major apolipoprotein species. To determine the specific role of SAA in the alteration of HDL in the absence of a generalized acute-phase response, acute-phase Saa1.1 transgene expression was directed via an inducible mouse metallothionein promoter. Elevated levels of SAA1.1 (28±9 mg/dL) comparable to a moderate acute-phase response were achieved over a 5-day period. SAA association with the HDL particles at this concentration did not significantly alter the apoA-I or HDL cholesterol levels or change the lipoprotein profiles in the transgenic mice compared with wild-type mice. In addition, we used adenoviral vectors to increase the SAA expression to levels seen in a major acute-phase response. Injection of adenovirus expressing the mouse SAA1.1 protein resulted in high-level expression (72±8 mg/dL) but did not alter apoA-I levels. However, the SAA associated with the HDL particle gave rise to significantly larger HDL particles (10%). Adenoviral expression of the constitutive SAA4 protein resulted in an increase in HDL size (10%) and an increase in very low density lipoprotein levels (20-fold) and triglyceride levels (1.7-fold). These studies suggest that increases in acute-phase SAA proteins alone are insufficient to alter HDL cholesterol or apoA-I levels during inflammation. A role for constitutive SAA4 in HDL–very low density lipoprotein interactions should be considered.

Key Words: amyloidosis • atherosclerosis • inflammation • apolipoproteins • adenoviruses

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