This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.More than one million people suffer from heart attacks and more than one-half million people die of heart disease in the United States each year. Low-density lipoprotein cholesterol (LDLC) plasma concentration is a major determinant of atherosclerotic risk. Individuals with high LDLC, the bad cholesterol, have a dramatically increased risk of heart disease compared with individuals with low LDLC. For many individuals, a high fat (HF) diet raises levels of LDLC in plasma. Both heredity and diet play major roles in determining an individual's cholesterol levels and thus one's risk of developing heart disease. The baboon is a well-established model for studying genetic mechanisms of heart disease. New genomic tools now make it possible to analyze all genes expressed in a tissue in a single experiment. These new tools also provide the means to analyze all of these data in the context of biological pathways in order to define genes that are most likely to play a role in the response to dietary fat and influence LDLC serum concentrations. This pilot study will: 1) identify hepatic genes with differential expression between low LDLC and high LDLC baboons; 2) identify genes with differential expression between low LDLC and high LDLC baboons in response to dietary fat; 3) identify biological pathways that are central to the hepatic dietary fat responsive genetic mechanism; and 4) define potential mechanisms by which these genes influence LDLC serum concentrations. The close physiological and genetic relationship between baboons and humans ensures that these data will be applicable to humans who have dramatically increased risk of heart disease due to high LDLC.Liver biopsies were collected during the low-cholesterol, low-fat (LCLF) diet and after 7 weeks on the HCHF diet. RNA samples from the liver biopsies were used to interrogate whole genome expression arrays (Illumina Beadchips).
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