KD (Keshan disease) is an endemic cardiomyopathy occurring only in China. Its pathogenesis is unclear till now. In the study, gene expression profiles of the PBMC (peripheral blood mononuclear cell) derived respec...KD (Keshan disease) is an endemic cardiomyopathy occurring only in China. Its pathogenesis is unclear till now. In the study, gene expression profiles of the PBMC (peripheral blood mononuclear cell) derived respectively from KD patients and healthy in KD areas were compared. Total RNA was isolated, amplified, labeled and hybridized to Agilent 4 ~ 44 K Whole Human Genome Oligonucleotide Microarray. Significant canonical pathways were analyzed by IPA (ingenuity pathway analysis) to identify differently expressed genes and pathways involved in the cardiovascular system development and function. Quantitative RT-PCR was applied to further validate our microarray results. Eighty-three up-regulated (ratios 〉 2.0) and nine down-regulated glycosyltransferase genes (ratios 〈 0.5) in PBMC in KD patients were detected by significance analysis of microarrays. Two significant canonical pathways from glycosyltransferase gene expression profiles were screened by IPA. The results of qRT-PCR show that four up-regulated (BMP 1/7/10 and FGF 18) and one down-regulated (BMP2) genes are consistent with those in microarray experiment, confirming the validity of the microarray data. Based on the results of the study, it is suggested that bone morphogenetic proteins and fibroblast growth factors might play an important role in the pathogenesis of KD. This further helps us to understand the pathogenesis of KD, as well as dilated cardiomyopathy.展开更多
文摘KD (Keshan disease) is an endemic cardiomyopathy occurring only in China. Its pathogenesis is unclear till now. In the study, gene expression profiles of the PBMC (peripheral blood mononuclear cell) derived respectively from KD patients and healthy in KD areas were compared. Total RNA was isolated, amplified, labeled and hybridized to Agilent 4 ~ 44 K Whole Human Genome Oligonucleotide Microarray. Significant canonical pathways were analyzed by IPA (ingenuity pathway analysis) to identify differently expressed genes and pathways involved in the cardiovascular system development and function. Quantitative RT-PCR was applied to further validate our microarray results. Eighty-three up-regulated (ratios 〉 2.0) and nine down-regulated glycosyltransferase genes (ratios 〈 0.5) in PBMC in KD patients were detected by significance analysis of microarrays. Two significant canonical pathways from glycosyltransferase gene expression profiles were screened by IPA. The results of qRT-PCR show that four up-regulated (BMP 1/7/10 and FGF 18) and one down-regulated (BMP2) genes are consistent with those in microarray experiment, confirming the validity of the microarray data. Based on the results of the study, it is suggested that bone morphogenetic proteins and fibroblast growth factors might play an important role in the pathogenesis of KD. This further helps us to understand the pathogenesis of KD, as well as dilated cardiomyopathy.