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Baboon Model for Dyslipidemia and Atherosclerosis

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The Baboon in Biomedical Research

Clinical manifestations of cardiovascular disease (CVD) remain the leading killer of men and women alike in the United States. The pedigreed baboon colony at the Southwest National Primate Research Center affords many advantages for the study of biological risk factors that influence the onset and progression of CVD. Not only is the baboon model amenable to experimentally induced atherosclerosis (McGill et al., 1976), but close phylogenetic and physiological similarities help to ensure that the results are pertinent to understanding human disease. This article focuses on established predictors of CVD risk, such as dyslipidemia and endothelial dysfunction, and the insights that have been gained from research with pedigreed baboons on the effects of diet and genotype, and their interactions, on these important predictive variables.

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References

  • Bojanovski, D., Alaupovic, P., Kelley, J. L., and Stout, C. (1978). Isolation and characterization of the major lipoprotein density classes of normal and diabetic baboon (Papio anubis) plasma. Atherosclerosis 31:481–487.

    Article  CAS  PubMed  Google Scholar 

  • Comuzzie, A. G., Martin, L. J., Cole, S. A., Rogers, J., Mahaney, M. C., Blangero, J., and VandeBerg, J. L. (2001). A quantitative trait locus for fat free mass in baboons localizes to a region homologous to human chromosome 6. Obes Res 9(Suppl. 3):71S (abstract).

    Google Scholar 

  • Cox, L. A., Jett, C., and Hixson, J. E. (1998). Molecular basis of an apolipoprotein[a] null allele: A splice site mutation is associated with deletion of a single exon. J. Lipid Res. 39:1319–1326.

    CAS  PubMed  Google Scholar 

  • Cox, L. A., Birnbaum, S., and VandeBerg, J. L. (2002). Identification of candidate genes regulating HDL cholesterol using a chromosomal region expression array. Genome Res. 12: 1693–1702.

    Article  CAS  PubMed  Google Scholar 

  • Cox, L. A., Birnbaum, S., Mahaney, M., and VandeBerg, J. L. (2005). Characterization of candidate genes regulating HDL-C using expression profiling. In: Xiong, X. G., Yan, Z. Z., and Liang, W. Y. (eds.), Proceedings of the XIII International Congress on Genes, Gene Families, and Isozymes. Medimond, Bologna Italy, pp. 177–180.

    Google Scholar 

  • Cox, L. A., Mahaney, M. C., VandeBerg, J. L., and Rogers, J. (2006). A second generation genetic linkage map of the baboon (Papio hamadryas) genome. Genomics 88:274–281.

    Article  CAS  PubMed  Google Scholar 

  • Cox, L. A., Birnbaum, S., Mahaney, M. C., Rainwater, D. L., Williams, J. T., and VandeBerg, J. L. (in press). Identification of promoter variants in baboon endothelial lipase that regulate HDL-cholesterol levels. Circulation.

    Google Scholar 

  • Eggen, D. A. (1974). Cholesterol metabolism in rhesus monkey, squirrel monkey, and baboon. J. Lipid Res. 15:139–145.

    CAS  PubMed  Google Scholar 

  • Geer, J. C., McGill, H. C., Jr., Robertson, W. B., and Strong, J. P. (1968). Histologic characteristics of coronary artery fatty streaks. Lab. Invest. 18:565–570.

    CAS  PubMed  Google Scholar 

  • Hasstedt, S. J., Wilson, D. E., Edwards, C. Q., Cannon, W. N., Carmelli, D., and Williams, R. R. (1983). The genetics of quantitative plasma Lp(a): Analysis of a large pedigree. Am. J. Med. Genet. 16:179–188.

    Article  CAS  PubMed  Google Scholar 

  • Hixson, J. E., Borenstein, S., Cox, L. A., Rainwater, D. L., and VandeBerg, J. L. (1988). The baboon gene for apolipoprotein A-I: Characterization of a cDNA clone and identification of DNA polymorphisms for genetic studies of cholesterol metabolism. Gene 74:483–490.

    Article  CAS  PubMed  Google Scholar 

  • Hixson, J. E., Britten, M. L., Manis, G. S., and Rainwater, D. L. (1989). Apolipoprotein(a) (Apo(a)) glycoprotein isoforms result from size differences in apo(a) mRNA in baboons. J. Biol. Chem. 264:6013–6016.

    CAS  PubMed  Google Scholar 

  • Kammerer, C. M., Hixson, J. E., and Mott, G. E. (1993). A DNA polymorphism for lecithin:cholesterol acyltransferase (LCAT) is associated with high density lipoprotein cholesterol concentrations in baboons. Atherosclerosis 98:153–163.

    Article  CAS  PubMed  Google Scholar 

  • Kammerer, C. M., Cox, L. A., Mahaney, M. C., Rogers, J., and Shade, R. E. (2001). Sodium-lithium countertransport activity is linked to chromosome 5 in baboons. Hypertension 37: 398–402.

    CAS  PubMed  Google Scholar 

  • Kammerer, C. M., Rainwater, D. L., Cox, L. A., Schneider, J. L., Mahaney, M. C., Rogers, J., and VandeBerg, J. L. (2002). Locus controlling LDL cholesterol response to dietary cholesterol is on baboon homologue of human chromosome 6. Arterioscler. Thromb. Vasc. Biol. 22: 1720–1725.

    Article  CAS  PubMed  Google Scholar 

  • Kammerer, C. M., Rainwater, D. L., Schneider, J. L., Cox, L. A., Mahaney, M. C., Rogers, J., and VandeBerg, J. F. (2003). Two loci affect angiotensin I-converting enzyme activity in baboons. Hypertension 41:854–859.

    Article  CAS  PubMed  Google Scholar 

  • Konigsberg, L. W., Blangero, J., Kammerer, C. M., and Mott, G. E. (1991). Mixed model segregation analysis of LDL-C concentration with genotype-covariate interaction. Genet. Epidemiol. 8:69–80.

    Article  CAS  PubMed  Google Scholar 

  • Kushwaha, R. S., and McGill, H. C., Jr. (1998). Diet, plasma lipoproteins and experimental atherosclerosis in baboons (Papio sp.). Hum. Reprod. Update 4:420–429.

    Article  CAS  PubMed  Google Scholar 

  • Kushwaha, R. S., Rainwater, D. L., Williams, M. C., Getz, G. S., and McGill, H. C., Jr. (1990). Impaired plasma cholesteryl ester transfer with accumulation of larger high density lipoproteins in some families of baboons (Papio sp.). J. Lipid Res. 31:965–973.

    CAS  PubMed  Google Scholar 

  • Kushwaha, R. S., Hasan, S. Q., McGill, H. C., Jr., Getz, G. S., Dunham, R. G., and Kanda, P. (1993). Characterization of cholesteryl ester transfer proltein inhibitor from plasma of baboons (Papio sp.). J. Lipid Res. 34:1285–1297

    CAS  PubMed  Google Scholar 

  • MacCluer, J. W., Kammerer, C. M., Blangero, J., Dyke, B., Mott, G. E., VandeBerg, J. L., and McGill, H. C., Jr. (1988). Pedigree analysis of HDL cholesterol concentration in baboons on two diets. Am. J. Hum. Genet. 43:401–413.

    CAS  PubMed  Google Scholar 

  • Mahaney, M. C., Rainwater, D. L., Rogers, J., Cox, L. A., Blangero, J., Almasy, L., VandeBerg, J. L., and Hixson, J. E. (1998). A genome search in pedigreed baboons detects a locus mapping to human chromosome 18q that influences variation in serum levels of HDL and its subtractions. Circulation 98:I–5(22) (abstract).

    Google Scholar 

  • Mahaney, M. C., Blangero, J., Rainwater, D. L., Mott, G. E., Comuzzie, A. G., MacCluer, J. W., and VandeBerg, J. L. (1999). Pleiotropy and genotype by diet interaction in a baboon model for atherosclerosis: A multivariate quantitative genetic analysis of HDL subfractions in two dietary environments. Arterioscler. Thromb. Vasc. Biol. 19:1134–1141.

    CAS  PubMed  Google Scholar 

  • McGill, H. C., Jr., and Kushwaha, R. S. (1995). Individuality of lipemic responses to diet. Can. J. Cardiol. 11(Suppl G):15G–27G.

    PubMed  Google Scholar 

  • McGill, H. C., Jr., Strong, J. P., Holman, R. L., and Werthessen, N. T. (1960). Arterial lesions in the Kenya baboon. Circ. Res. 8:670–679.

    Google Scholar 

  • McGill, H. C., Jr., Mott, G. E., and Bramblett, C. A. (1976). Experimental atherosclerosis in the baboon. Primates Med. 9:41–65.

    CAS  PubMed  Google Scholar 

  • McGill, H. C., Jr., McMahan, A., Kruski, A. W., Kelley, J. L., and Mott, G.E. (1981a). Responses of serum lipoproteins to dietary cholesterol and type of fat in the baboon. Arteriosclerosis 1:337–344.

    Google Scholar 

  • McGill, H. C., Jr., McMahan, C. A., Kruski, A. W., and Mott, G. E. (1981b). Relationship of lipoprotein cholesterol concentrations to experimental atherosclerosis in baboons. Arteriosclerosis 1:3–12.

    Google Scholar 

  • McGill, H. C., Jr., Carey, K. D., McMahan, C. A., Marinez, Y. N., Cooper, T. E., Mott, G. E., and Schwartz, C. J. (1985). Effects of two forms of hypertension on atherosclerosis in the hyperlipidemic baboon. Arteriosclerosis 5:481–493.

    CAS  PubMed  Google Scholar 

  • McGill, H. C. Jr., McMahan, C. A., Kushwaha, R. S., Mott, G. E., and Carey, K. D. (1986). Dietary effects on serum lipoproteins of dyslipoproteinemic baboons with high HDL1. Arteriosclerosis 6:651–663.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L. (1994). Genetic effects on dietary response of Lp(a) concentrations in baboons. Chem. Phys. Lipids 67/68:199–205.

    Article  Google Scholar 

  • Rainwater, D. L., and Manis, G. S. (1988). Immunochemical characterization and quantitation of lipoprotein (a) in baboons. Development of an assay depending on two antigenically distinct proteins. Atherosclerosis 73:23–31.

    Article  CAS  PubMed  Google Scholar 

  • Rainwater, D. L., and Lanford, R. E. (1989). Production of lipoprotein(a) by primary baboon hepatocytes. Biochim. Biophys. Acta 1003:30–35.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Manis, G. S., and Kushwaha, R. S. (1986). Characterization of an unusual lipoprotein similar to human lipoprotein a isolated from the baboon, Papio sp. Biochim. Biophys. Acta 877:75–78.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Manis, G. S., and VandeBerg, J. L. (1989). Hereditary and dietary effects on apolipoprotein[a] isoforms and Lp[a] in baboons. J. Lipid Res. 30:549–558.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Blangero, J., Hixson, J. E., Birnbaum, S., Mott, G. E., and VandeBerg, J. L. (1992). A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons. Arterioscler. Thromb. 12:682–690.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Kammerer, C. M., Hixson, J. E., Carey, K. D., Rice, K. S., Dyke, B., VandeBerg, J. F., Slifer, S. H., Atwood, L. D., McGill, H. C., Jr., and VandeBerg, J. L. (1998). Two major loci control variation in β-lipoprotein cholesterol and response to dietary fat and cholesterol in baboons. Arterioscler. Thromb. Vasc. Biol. 18:1061–1068.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Almasy, L., Blangero, J., Cole, S. A., VandeBerg, J. L., MacCluer, J. W., and Hixson, J. E. (1999). A genome search identifies major quantitative trait loci on human chromosomes 3 and 4 that influence cholesterol concentrations in small LDL particles. Arterioscler. Thromb. Vasc. Biol. 19:777–783.

    CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Kammerer, C. M., Carey, K. D., Dyke, B., VandeBerg, J. F., Shelledy, W. R., Moore, P. H., Jr., Mahaney, M. C., McGill, H. C., Jr., and VandeBerg, J. L. (2002a). Genetic determination of HDL variation and response to diet in baboons. Atherosclerosis 161: 335–343.

    Google Scholar 

  • Rainwater, D. L., Kammerer, C. M., Cox, L. A., Rogers, J., Carey, K. D., Dyke, B., Mahaney, M. C., McGill, H. C., Jr., and VandeBerg, J. L. (2002b). A major gene influences variation in large HDL particles and their response to diet in baboons. Atherosclerosis 163:241–248.

    Google Scholar 

  • Rainwater, D. L., Kammerer, C. M., Mahaney, M. C., Rogers, J., Cox, L. A., Schneider, J. L., and VandeBerg, J. L. (2003). Localization of genes that control LDL size fractions in baboons. Atherosclerosis168:15–22.

    Article  CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Mahaney, M. C., Wang, X. L., Rogers, J., Cox, L. A., and VandeBerg, J. L. (2005). Determinants of variation in serum paraoxonase enzyme activity in baboons. J. Lipid Res. 46:1450–1456.

    Article  CAS  PubMed  Google Scholar 

  • Rainwater, D. L., Mahaney, M. C., VandeBerg, J. L., and Wang, X. L. (in press). Vitamin E dietary supplementation significantly affects multiple risk factors for cardiovascular disease in baboons. Am. J. Clin. Nutr.

    Google Scholar 

  • Robertson, W. B., Geer, J. C., Strong, J. P., and McGill, H. C., Jr. (1963). The fate of the fatty streak. Exp. Mol. Pathol. 52(Suppl. I):28–39.

    PubMed  Google Scholar 

  • Rogers, J., Mahaney, M. C., Witte, S. M., Nair, S., Newman, D., Wedel, S., Rodriguez, L. A., Rice, K. S., Slifer, S. H., Perelygin, A., Slifer, M., Palladino-Negro, P., Newman, T., Chambers, K., Joslyn, G., Parry, P., and Morin, P. A. (2000). A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms. Genomics 67:237–247.

    Article  CAS  PubMed  Google Scholar 

  • Ross, R. (1999). Atherosclerosis--an inflammatory disease. N. Engl. J. Med. 340:115–126.

    Article  CAS  PubMed  Google Scholar 

  • Shi, Q., Aida, K., VandeBerg, J. L., and Wang, X. L. (2004a). Passage-dependent changes in baboon endothelial cells--relevance to in vitro aging. DNA Cell Biol. 23:502–509.

    Google Scholar 

  • Shi, Q., Wang, J., Wang, X. L., and VandeBerg, J. L. (2004b). Comparative analysis of vascular endothelial cell activation by TNF-α and LPS in humans and baboons. Cell Biochem. Biophys. 40:289–304.

    Google Scholar 

  • Shi, Q., VandeBerg, J. F., Jett, C., Rice, K., Leland, M. M., Talley, L., Kushwaha, R. S., Rainwater, D. L., VandeBerg, J. L., and Wang, X. L. (2005). Arterial endothelial dysfunction in baboons fed a high-cholesterol, high-fat diet. Am. J. Clin. Nutr. 82:751–759.

    CAS  PubMed  Google Scholar 

  • Shi, Q., Hubbard, G. B., Kushwaha, R. S., Rainwater, D. L., Thomas, C. A., III, Leland, M. M., VandeBerg, J. L., Wang, X. L. (2007). Endothelial senescence after high-cholesterol, high-fat diet challenge in baboons. Am. J. Physiol. Heart Circ. Physiol. 292:H2913–H2920.

    Article  CAS  PubMed  Google Scholar 

  • Singh, A. T. K., Rainwater, D. L., Kammerer, C. M., Sharp, R. M., Poushesh, M., Shelledy, W. R., and VandeBerg, J. L. (1996). Dietary and genetic effects on LDL size measures in baboons. Arterioscler. Thromb. Vasc. Biol. 16:1448–1453.

    CAS  PubMed  Google Scholar 

  • Utermann, G. (1989). The mysteries of lipoprotein(a). Science 246:904–910.

    Article  CAS  PubMed  Google Scholar 

  • Vinson, A., Mahaney, M. C., Cox, L. A., Rogers, J., VandeBerg, J. L., and Rainwater, D. L. (in press). A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors. Atherosclerosis.

    Google Scholar 

  • Wang, Q. F., Liu, X., O’Connell, J., Peng, Z., Krauss, R. M., Rainwater, D. L., VandeBerg, J. L., Rubin, E. M., Cheng, J. F., and Pennacchio, L. A. (2004a). Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. Hum. Mol. Genet. 13:1049–1056.

    Google Scholar 

  • Wang, X. L., Wang, J., Shi, Q., Carey, K. D., and VandeBerg, J. L. (2004b). Arterial wall-determined risk factors to vascular diseases: A nonhuman primate model. Cell Biochem. Biophys. 40:371–388.

    Google Scholar 

  • White, A. L., and Lanford, R. E. (1994). Cell surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes. J. Biol. Chem. 269:28716–28723.

    CAS  PubMed  Google Scholar 

  • White, A. L., Rainwater, D. L., and Lanford, R. E. (1993). Intracellular maturation of apolipoprotein[a] and assembly of lipoprotein[a] in primary baboon hepatocytes. J. Lipid Res. 34:509–517.

    CAS  PubMed  Google Scholar 

  • White, A. L., Hixson, J. E., Rainwater, D. L., Lanford, R. E. (1994a). Molecular basis for “null” lipoprotein(a) phenotypes and the influence of apolipoprotein(a) size on plasma lipoprotein(a) level in the baboon. J. Biol. Chem. 269:9060–9066.

    Google Scholar 

  • White, A. L., Rainwater, D. L., Hixson, J. E., Estlack, L. E., and Lanford, R. E. (1994b). Intracellular processing of apo(a) in primary baboon hepatocytes. Chem. Phys. Lipids 67/68:123–133.

    Google Scholar 

  • White, A. L., Guerra, B., and Lanford, R. E. (1997). Influence of allelic variation on apolipoprotein(a) folding in the endoplasmic reticulum. J. Biol. Chem. 272:5048–5055.

    Article  CAS  PubMed  Google Scholar 

  • White, A. L., Guerra, B., Wang, J., and Lanford, R. E. (1999). Presecretory degradation of apolipoprotein[a] is mediated by the proteasome pathway. J. Lipid Res. 40:275–286.

    CAS  PubMed  Google Scholar 

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Rainwater, D.L., VandeBerg, J.L. (2009). Baboon Model for Dyslipidemia and Atherosclerosis. In: VandeBerg, J.L., Williams-Blangero, S., Tardif, S.D. (eds) The Baboon in Biomedical Research. Developments in Primatology: Progress and Prospects. Springer, New York, NY. https://doi.org/10.1007/978-0-387-75991-3_11

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