tailieunhanh - Báo cáo sinh học: " Improvement of cardiac contractile function by peptide-based inhibition of NF-B in the utrophin/dystrophin-deficient murine model of muscular dystrophy"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Improvement of cardiac contractile function by peptide-based inhibition of NF- B in the utrophin/dystrophin-deficient murine model of muscular dystrophy | Delfin et al. Journal of Translational Medicine 2011 9 68 http content 9 1 68 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Improvement of cardiac contractile function by peptide-based inhibition of NF- .-B in the utrophin dystrophin-deficient murine model of muscular dystrophy Dawn A Delfin1 Ying Xu2 Jennifer M Peterson33 Denis C Guttridge33 Jill A Rafael-Fortney13 and Paul ML Janssen2 3 Abstract Background Duchenne muscular dystrophy DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD Nemo Binding Domain targeted at blunting Nuclear Factor kB NF-kB signaling reduces inflammation enhances myofiber regeneration and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin double knockout dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure including myocyte degeneration an impaired force-frequency response and a severely blunted p-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as p-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition we studied histopathological and inflammatory markers in these mice. Results At baseline conditions active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also .

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