Impact of Hyperhomocysteinemia on Cardiac Gene Expression in Pregnant Rats

Abstract

Hyperhomocysteinemia (HHcy) causes cardiovascular dysfunction during pregnancy. We have previously shown that HHcy disrupts the regulation of O2 consumption in the heart by lowering NO bioavailability through the generation of superoxide. Presently, we explored the molecular effects of HHcy during pregnancy. Pregnant SD rats were fed with 10g/L methionine in drinking water for 20 days to increase plasma homocysteine (Hcy) (3.0±1.2 to 14.6±8.9 uM). mRNA microarray analysis of left ventricle tissue revealed significant changes in 242 genes (p<0.05, > ±1.5). We grouped differentially expressed genes into different functional categories, and the results showed a wide range of distribution of expression patterns within the functional groups. For example, some cell structure/motility genes were upregulated, including Kruppel‐like factor, histone deacetylase 1, myosin 1b, and ARP2 actin‐related protein 2. We have also seen several oxidative stress‐related genes, such as hypoxia up‐regulated 1 and ischemia related factor up‐regulated. Metabolism genes such as pyruvate dehydrogenase phosphatase isoenzyme 2 and fatty acid transporter 4 were differentially regulated.ConclusionHHcy triggers cardiac gene expression changes during pregnancy, suggesting an underlying mechanism behind the effects of HHcy.