Dilated Cardiomyopathy Mutations in Thin Filament Regulatory Proteins Reduce Contractility, Suppress Systolic Ca2+ & Activate NFAT & AKT Signalling.
Dilated Cardiomyopathy Mutations in Thin Filament Regulatory Proteins Reduce Contractility, Suppress Systolic Ca2+ &Activate NFAT &AKT Signalling. Am J Physiol Heart Circ Physiol. 2020 Jul 03;: Authors: Robinson P, Sparrow AJ, Patel S, Malinowska M, Reilly SN, Zhang YH, Casadei B, Watkins H, Redwood C Abstract Dilated cardiomyopathy (DCM) is clinically characterised by dilated ventricular cavities and reduced ejection fraction, leading to heart failure and increased thromboembolic risk. Mutations in thin filament regulatory proteins can cause DCM and have been shown in vitro to reduce contractility and myofilament Ca2+-affinity. In this work we have studied the functional consequences of mutations in cardiac troponin T (R131W), cardiac troponin I (K36Q) and α-tropomyosin (E40K) using adenovirally transduced isolated guinea pig left ventricular cardiomyocytes. We find significantly reduced fractional shortening with reduced systolic Ca2+. We also observe slowed contraction and Ca2+-reuptake times, which contrast with some findings in murine models of myofilament Ca2+-desensitisation. We also observe increased sarco-endoplasmic reticulum (SR) Ca2+ load and smaller fractional SR Ca2+ release. This corresponds to a reduction in SR Ca2+-ATPase activity and increase in Sodium-Calcium Exchanger activity. The disequilibrium of Ca2+ handling promotes dephosphorylation and nuclear translocation of the Nuclear-Factor-of-Activated T-cells (NFAT), with ...
Publication date: Available online 2 August 2020Source: Journal of Clinical &Translational EndocrinologyAuthor(s): Masahiro Usui, Mamiko Tanaka, Hironori Takahashi
Publication date: Available online 2 August 2020Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Xuejun Xu, Zichen Luo, Yu He, Jinjun Shan, Jianming Guo, Jianping Li
Conclusion CCS patients have a distinctive fingerprint of exhaled breath, and analysis by BIONOTE-V has the potential for identifying these patients. Moreover, it seems that this technique can correctly identify patients according to anatomical disease severity at ICA. If the preliminary data of this proof of concept study will be confirmed, this rapid and noninvasive diagnostic tool able to identify CCS might have an impact in routine clinical practice.
We examined the effects of sacubitril/valsartan on cardiac remodeling and their correlation with heart failure duration in patients enrolled in our heart failure clinic from March 2017 to December 2019. Methods Echocardiographic and clinical/laboratory data were collected at baseline and at 6-month and 12-month follow-up visits in 69 patients (age 67 ± 12 years, disease duration 8.4 ± 5.8 years, 93% men). Results At both time points, mean NYHA class, NT-proBNP level, LVEF, LV end-systolic volume, and estimated systolic pulmonary pressure significantly (P
Conclusion Cardiac involvement is common and has significant prognostic implications in the evaluated patients with p.Glu89Gln mutation. Heart failure and rhythm disturbances are the main causes of death. An earlier identification of the disease is crucial to improve prognosis.
Conclusions In our study, only a few ECG voltage criteria used for the detection of LVH in clinical practice showed an acceptable performance in the HCM population. Further studies are needed to clarify the role of ECG for LVH detection in HCM patients.
CONCLUSIONS: Sodium divalproate, frequently used in the treatment of bipolar disorder, is a rare cause of eosinophilic lung disease, even years after its introduction. Rapid diagnosis and withdrawal of treatment led to complete resolution in the reported case. PMID: 32739035 [PubMed - as supplied by publisher]
Benefits were seen, however, in patients starting with poor quality of life, suggesting a need for dynamic palliative care interventions that can readily adapt to the patient's needs.Medscape Medical News
Publication date: Available online 2 August 2020Source: Ticks and Tick-borne DiseasesAuthor(s): Cheyne Kurokawa, Sukanya Narasimhan, Aurobind Vidyarthi, Carmen J. Booth, Sameet Mehta, Lea Meister, Husrev Diktas, Norma Strank, Geoffrey E. Lynn, Kathy DePonte, Joseph Craft, Erol Fikrig
In conclusion, our findings demonstrate that ZNF307 ameliorates pressure overload–induced cardiac hypertrophy by inhibiting the activity of NF-κB–signaling pathway.