Decreased expression of neurotrophic tyrosine receptor kinase 3 is associated with the outflow tract defect of human tetralogy of Fallot

Background The molecular mechanism of human tetralogy of Fallot （TOF） is incompletely defined. Animal models have suggested that neurotrophic tyrosine receptor kinase 3 （NTRK3） might be associated with the outflow tract defect, similar to that seen in human TOF, however, the expression pattern of NTRK3 in human TOF heart tissues has never been investigated. Methods Quantitative real-time PCR （qRT-PCR） and immunohistochemistry were applied to detect NTRK3 mRNA and protein levels in right ventricular outflow tract tissue samples of TOF patients, ventricular septal defect （VSD） patients and normal control infants （n=10 in each group）. Results qRT-PCR analysis indicated that NTRK3 mRNA levels were significantly decreased in the TOF group compared to the VSD group （0.024±0.003 vs 0.085±0.004, P=0.022） and the normal control group （0.024±0.003 vs 0.091±0.002, P=0.006）. Quantitative immunohistochemical analysis showed that NTRK3 protein was mainly localized in the myocardium cytoplasm in all 3 groups. The immunoreactivity of NTRK3 protein was again significantly lower in the TOF group compared to the VSD group （1.42±0.62 vs 14.12±1.83, P=0.023） and the control group （1.42±0.62 vs 16.25±2.31, P=-0.008）. The expression of NTRK3 in the VSD group and in the control group showed no significant differences at both mRNA and protein levels. Conclusions Insufficient expression of NTRK3 is associated with the outflow tract defect of human tetralogy of Fallot and may contribute to the progression of this defect. Chin Med J 2009; 122（2）： 153-157

Microarray-bioinformatics analysis of altered genomic expression profiles between human fetal and infant myocardium

Background The physiological differences between fetal and postnatal heart have been well characterized at the cellular level. However, the genetic mechanisms governing and regulating these differences have only been partially elucidated. Elucidation of the differentially expressed genes profile before and after birth has never been systematically proposed and analyzed. Methods The human oligonucleotide microarray and bioinformatics analysis approaches were applied to isolate and classify the differentially expressed genes between fetal and infant cardiac tissue samples. Quantitative real-time PCR was used to confirm the results from the microarray. Results Two hundred and forty-two differentially expressed genes were discovered and classified into 13 categories, including genes related to energy metabolism, myocyte hyperplasia, development, muscle contraction, protein synthesis and degradation, extracellular matrix components, transcription factors, apoptosis, signal pathway molecules, organelle organization and several other biological processes. Moreover, 95 genes were identified which had not previously been reported to be expressed in the heart. Conclusions The study systematically analyzed the alteration of the gene expression profile between the human fetal and infant myocardium. A number of genes were discovered which had not been reported to be expressed in the heart. The data provided insight into the physical development mechanisms of the heart before and after birth.