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. 2018 Feb;47(1):3-17.
doi: 10.1111/jmp.12283. Epub 2017 Jun 16.

Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance

Affiliations

Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance

Michael C Mahaney et al. J Med Primatol. 2018 Feb.

Abstract

Background: The purpose of this study was to determine whether dietary manipulation can reliably induce early-stage atherosclerosis and clinically relevant changes in vascular function in an established, well-characterized non-human primate model.

Methods: We fed 112 baboons a high-cholesterol, high-fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy.

Results: We observed evidence of atherosclerosis in all but one baboon fed the two-year challenge diet. CVD risk biomarkers, the prevalence, size, and complexity of arterial lesions, plus consequent arterial stiffness, were increased in comparison with dietary control animals.

Conclusions: Feeding baboons a high-cholesterol, high-fat diet for two years reliably induces atherosclerosis, with risk factor profiles, arterial lesions, and changes in vascular function also seen in humans.

Keywords: cardiovascular disease; high-fat diet; non-human primate.

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Figures

Figure 1
Figure 1
Atherosclerotic lesions in three arteries from baboons after being stained with lipophilic Sudan IV. Columns: Common iliac artery (Left), thoracic aorta (center), and aortic arch (right). Rows 1 and 2: Control diet animals with no (row 1) and highest (row 2) total percent area affected. Experimental diet animals with lowest (row 3) and highest (row 4) percent total area affected.
Fig. 2
Fig. 2
A–2J. Serum biomarkers of lipid/lipoprotein metabolism, inflammation, and oxidative stress measured at three time-points in 112 baboons in the two-year HCHF diet challenge study: at baseline (Week 0, LCLF diet), seven weeks into the HCHF diet challenge (Week 7), and at the end of the HCHF dietary challenge (Week 104). Figure 2A, concentrations of major lipoproteins, apolipoproteins, and triglycerides; Figure 2B. concentrations of HDLC fractions; Figure 2C, concentrations of V+LDLC fractions; Figure 2D, Hmed and Bmed; Figure 2E, concentration of OxLDL; Figure 2F, activity of lipoprotein associated enzymes, LpPLA2, PON-para, and PON-aryl; Figure 2G, concentrations of CRP; Figure 2H, concentrations of IL8; Figure 2I, vWF as percentage of international standard value; and Figure 2J, TAS.
Fig. 2
Fig. 2
A–2J. Serum biomarkers of lipid/lipoprotein metabolism, inflammation, and oxidative stress measured at three time-points in 112 baboons in the two-year HCHF diet challenge study: at baseline (Week 0, LCLF diet), seven weeks into the HCHF diet challenge (Week 7), and at the end of the HCHF dietary challenge (Week 104). Figure 2A, concentrations of major lipoproteins, apolipoproteins, and triglycerides; Figure 2B. concentrations of HDLC fractions; Figure 2C, concentrations of V+LDLC fractions; Figure 2D, Hmed and Bmed; Figure 2E, concentration of OxLDL; Figure 2F, activity of lipoprotein associated enzymes, LpPLA2, PON-para, and PON-aryl; Figure 2G, concentrations of CRP; Figure 2H, concentrations of IL8; Figure 2I, vWF as percentage of international standard value; and Figure 2J, TAS.

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