Abstract
MicroRNAs are short non-coding RNAs that regulate gene expression. Several microRNAs, useful for coronary artery disease assessment, have previously been identified. MicroRNA-33 is located within SREBP introns and controls cholesterol homeostasis. In order to find the possibility of microRNA-33 as a potential biomarker in high cholesterol disease, we developed a mouse model for coronary heart disease by feeding mice with a high-fat diet. The expression differences of microRNA-33, SREBP and ABCA1 genes in the liver, muscle, and lipid tissues were compared between a high-cholesterol group and control group in mice. The results showed that ABCA1 was up-regulated by high cholesterol conditions in liver, muscle and lipid tissues. SREBP1C was up-regulated by high cholesterol conditions in the liver and lipid tissues and down-regulated by high cholesterol conditions in the muscle tissue. MicroRNA-33 and SREBP2 were down-regulated by high cholesterol conditions in the liver and muscle tissues and up-regulated by high cholesterol conditions in the lipid tissue. Our study suggests that antisense therapeutic targeting of microRNA-33 may be a potential biomarker for cardiovascular disease.
Highlights
Cholesterol plays key role in many physiological process, and aberrant cholesterol content has been linked to disease, including coronary atherosclerosis and other diseases (Maxfield and Tabas, 2005; Moller and Kaufman, 2005)
SREBP1C is up-regulated by high cholesterol conditions in the liver and lipid tissues and down-regulated by high cholesterol conditions in the muscle tissue
MicroRNA-33 and SREBP2 are down-regulated by high cholesterol conditions in the liver and muscle tissues and upregulated by high cholesterol conditions in the lipid tissue
Summary
Cholesterol plays key role in many physiological process, and aberrant cholesterol content has been linked to disease, including coronary atherosclerosis and other diseases (Maxfield and Tabas, 2005; Moller and Kaufman, 2005). Circulating microRNAs are present within body fluids in a stable, cell-free form, and differing microRNA expression levels can be identified in various stages of coronary artery disease (CAD). MicroRNA-33a and microRNA-33b (the latter being present in primates but absent in rodents and lower species) are located within the introns of the sterol regulatory element binding protein (SREBP)-encoding genes. The SREBP cooperates with the proteins to control cholesterol homeostasis, fatty acid levels and expression of genes related to fat metabolism (Brown and Goldstein, 1997; Horie et al, 2010). SREBP-1 regulated the gene expression which related to fatty acid synthesis
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