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Rationale: The ability of the human heart to regenerate large quantities of myocytes remains controversial, and the extent of myocyte renewal claimed by different laboratories varies from none to nearly 20% per year. Objective: To address this issue, we examined the percentage of myocytes, endothelial cells, and fibroblasts labeled by iododeoxyuridine in(More)
Protein misfolding and aberrant aggregation are associated with many severe disorders, such as neural degenerative diseases, desmin-related myopathy (DRM), and congestive heart failure. Intrasarcoplasmic amyloidosis and increased ubiquitinated proteins are observed in human failing hearts. The pathogenic roles of these derangements in the heart remain(More)
BACKGROUND Anthracyclines are the most effective drugs available in the treatment of neoplastic diseases; however, they have profound consequences on the structure and function of the heart, which over time cause a cardiomyopathy that leads to congestive heart failure. METHODS AND RESULTS Administration of doxorubicin in rats led to a dilated myopathy,(More)
Ubiquitin-proteasome system (UPS) mediated proteolysis is responsible for the degradation of majority of cellular proteins, thereby playing essential roles in maintaining cellular homeostasis and regulating a number of cellular functions. UPS dysfunction was implicated in the pathogenesis of numerous disorders, including neurodegenerative disease, muscular(More)
BACKGROUND Cardiac stem cells (CSCs) delivered to the infarcted heart generate a large number of small fetal-neonatal cardiomyocytes that fail to acquire the differentiated phenotype. However, the interaction of CSCs with postmitotic myocytes results in the formation of cells with adult characteristics. METHODS AND RESULTS On the basis of results of in(More)
The presence of increased ubiquitinated proteins and amyloid oligomers in failing human hearts strikingly resembles the characteristic pathology in the brain of many neurodegenerative diseases. The ubiquitin-proteasome system (UPS) is responsible for degradation of most cellular proteins and plays essential roles in virtually all cellular processes. UPS(More)
RATIONALE Two categories of cardiac stem cells (CSCs) with predominantly myogenic (mCSC) and vasculogenic (vCSC) properties have been characterized in the human heart. However, it is unknown whether functionally competent CSCs of both classes are present in the myocardium of patients affected by end-stage cardiac failure, and whether these cells can be(More)
The ubiquitin proteasome system (UPS) degrades abnormal proteins and most unneeded normal proteins, thereby playing a critical role in protein homeostasis in the cell. Proteasome inhibition is effective in treating certain forms of cancer, while UPS dysfunction is increasingly implicated in the pathogenesis of many severe and yet common diseases. It has(More)
The ubiquitin-proteasome system (UPS) is responsible for turnover of most cellular proteins in eukaryotes. Protein degradation by the UPS serves quality control and regulatory functions. Proteasome inhibition showed great promise in effectively treating cancer and restenosis. UPS dysfunction in cardiac hypertrophy and failure has recently been suspected but(More)
The ubiquitin-proteasome system (UPS) is responsible for the degradation of most cellular proteins. Alterations in cardiac UPS, including changes in the degradation of regulatory proteins and proteasome functional insufficiency, are observed in many forms of heart disease and have been shown to play an important role in cardiac pathogenesis. In the past(More)