Cardiomyocyte proteostasis is mediated by the ubiquitin/proteasome system (UPS) and autophagy/lysosome system and is fundamental for cardiac adaptation to both physiologic (e.g., exercise) and pathologic (e.g., pressure overload) stresses. Both the UPS and autophagy/lysosome system exhibit reduced efficiency as a consequence of aging, and dysfunction in these systems is associated with cardiomyopathies. The musclespecific ubiquitin ligase atrogin-1 targets signaling proteins involved in cardiac hypertrophy for degradation. Here, using atrogin-1 KO mice in combination with in vivo pulsed stable isotope labeling of amino acids in cell culture proteomics and biochemical and cellular analyses, we identified charged multivesicular body protein 2B (CHMP2B), which is part of an endosomal sorting complex (ESCRT) required for autophagy, as a target of atrogin-1-mediated degradation. Mice lacking atrogin-1 failed to degrade CHMP2B, resulting in autophagy impairment, intracellular protein aggregate accumulation, unfolded protein response activation, and subsequent cardiomyocyte apoptosis, all of which increased progressively with age. Cellular proteostasis alterations resulted in cardiomyopathy characterized by myocardial remodeling with interstitial fibrosis, with reduced diastolic function and arrhythmias. CHMP2B downregulation in atrogin-1 KO mice restored autophagy and decreased proteotoxicity, thereby preventing cell death. These data indicate that atrogin-1 promotes cardiomyocyte health through mediating the interplay between UPS and autophagy/lysosome system and its alteration promotes development of cardiomyopathies.
Background: Coronavirus Disease 2019 (COVID-19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality. The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID-19 patients. Information on the benefit/risk ratio of this approach is still lacking. Objective: To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug.
Apart from Lε, the inter-vendor agreement of Rε, Cε and Aε measured with Artida and VividE9 was poor. Reference values should be specific for each system and baseline and follow-up data in longitudinal studies should be obtained using the same 3D STE platform.
Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.
Angiographically detected coronary aneurysms (i.e., coronary segment greater then 1.5 times the normal artery) have an incidence of 0.3%-4.9% among patients undergoing coronary angiography and have been reported after an intervention procedure with a frequency of 2%-10%. The indication for treatment and the best modality still need to be defined. Some authors reported the successful treatment of coronary aneurysms with the polytetrafluoroethylene (PTFE)-covered stent implantation, supporting the role of this strategy. In our institution, from September 1997 to December 1999 eight PTFE-covered stents were implanted to treat seven coronary aneurysms in seven patients. All aneurysms were successfully treated by the PTFE-covered stent. In one case, there was the necessity of an additional PTFE stent to cover the aneurysm completely. In no case did the loss of stent occur. No in-hospital MACE occurred. At 35 +/- 8 (21-44) months, six patients were symptom-free. Angiographic follow-up was performed in all patients at 10 +/- 6 months. Restenosis occurred in one patient (14%) who had repeat percutaneous coronary interventions. This preliminary experience suggests that PTFE-covered stent may be useful in the treatment of coronary artery aneurysms.
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