摘要
Progressive deterioration of physical work capacity in congestive heart failure (CHF) is often attributed to ongoing skeletal muscle atrophy and abnormalities in muscle metabolism. The purpose of the present study was to investigate if mutations in the p53 gene thought to be a promotor of apoptosis are involved in intrinsic apoptotic abnormalities in skeletal muscle of patients (pts) with CHF. Percutaneous needle biopsy from the m. vastus lateralis were obtained from 19 pts with CHF (LV EF 25%±10%). Single strand confirmation polymorphism analysis of polymerase chain reation products (PCR SSCP analysis) was used for detection of mutations in exon 5 8 of the p53 gene in skeletal Heart Center, University Leipzig, Germany (Yu JT, Adams V, Fiehn E, Schuler G and Hambrecht R) Institut of Pathology, University Freiburg, Germany (Ye J and Riede U)muscle cells. Four of 19 muscle specimens (21%) showed mobility shifts. To characterize the nuleotide sequence alterations specimens were examined further by direct sequence analysis of PCR product. Two of four specimens showing a band shift in the SSCP analysis exhibited a mutated p53 sequence. Sequence analysis revealed that these alteratons were point mutation exon 8 (14482, G→A) and deletion in exon 5 (13143 13157). A high frequency of p53 mutations was detected in skeletal muscle cells of patients with chronic heart failure. These findings suggest a role for apoptosis in the progression of intrinsic skeletal muscle abnormalities and consequently of exercise intolerance in chronic heart failure.
Progressive deterioration of physical work capacity in congestive heart failure (CHF) is often attributed to ongoing skeletal muscle atrophy and abnormalities in muscle metabolism. The purpose of the present study was to investigate if mutations in the p53 gene thought to be a promotor of apoptosis are involved in intrinsic apoptotic abnormalities in skeletal muscle of patients (pts) with CHF. Percutaneous needle biopsy from the m. vastus lateralis were obtained from 19 pts with CHF (LV EF 25%±10%). Single strand confirmation polymorphism analysis of polymerase chain reation products (PCR SSCP analysis) was used for detection of mutations in exon 5 8 of the p53 gene in skeletal Heart Center, University Leipzig, Germany (Yu JT, Adams V, Fiehn E, Schuler G and Hambrecht R) Institut of Pathology, University Freiburg, Germany (Ye J and Riede U)muscle cells. Four of 19 muscle specimens (21%) showed mobility shifts. To characterize the nuleotide sequence alterations specimens were examined further by direct sequence analysis of PCR product. Two of four specimens showing a band shift in the SSCP analysis exhibited a mutated p53 sequence. Sequence analysis revealed that these alteratons were point mutation exon 8 (14482, G→A) and deletion in exon 5 (13143 13157). A high frequency of p53 mutations was detected in skeletal muscle cells of patients with chronic heart failure. These findings suggest a role for apoptosis in the progression of intrinsic skeletal muscle abnormalities and consequently of exercise intolerance in chronic heart failure.
