scholarly journals Desmin Correlated with Cx43 May Facilitate Intercellular Electrical Coupling during Chronic Heart Failure

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Junxian Cao ◽  
Qianping Gao ◽  
Hongyan Chen ◽  
Can Wang ◽  
Qiuju Zhang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocytes ◽  
Connexin 43 ◽  
Electrical Coupling ◽  
Intermediate Filament Proteins ◽  
Skeletal Myoblasts ◽  
Activation Rate ◽  
Patients With Heart Failure ◽  
Amyloid Polyneuropathy ◽  
Long Term Prognosis

Desmin is one of five major intermediate filament proteins in cardiomyocytes. Desmin contributes to the maintenance of healthy muscle. The desmin content in cardiomyocytes directly affects the long-term prognosis of patients with heart failure, and lack of desmin leads to myocyte contractile dysfunction. However, the mechanism is elusive. In this study, we measured desmin expression using western blotting and qPCR in the failed hearts of human patients and rats. Our results showed that desmin content was reduced at the protein level in failed hearts and isolated cardiomyocytes. The association of desmin and the gap junction proteins connexin 43 (Cx43) and zonula occludens-1 (ZO-1) was also investigated. Immunoprecipitation assay showed that desmin was associated with Cx43 in cardiomyocytes. To compare the electrical integration of skeletal myoblasts in cocultures with cardiac myocytes, familial amyloid polyneuropathy (FAP) activation rate was found in 33% desmin overexpressing skeletal myoblasts. Desmin not only affected Cx43 and ZO-1 expression but also facilitated the complex of Cx43 and ZO-1 in skeletal myoblasts, which enhanced cell-to-cell electrical coupling of skeletal myoblasts with cardiac myocytes. Desmin has potential as a novel therapeutic target for heart failure. Preservation of desmin may attenuate heart failure.

Abstract 71: STAT3 Affects Myofibrillar Structure and Its Loss May Contribute to Heart Failure in Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Fouad Zouein ◽  
Carlos Zgheib ◽  
John Fuseler ◽  
John E Hall ◽  
Mazen Kurdi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocytes ◽  
Transcriptional Activity ◽  
Cardiac Myocyte ◽  
Early Stage ◽  
Systolic Dysfunction ◽  
Wild Type ◽  
Patients With Heart Failure ◽  
Protective Proteins ◽  
Fractional Shortening

How hypertension causes heart failure is not known. Since patients with heart failure have reduced cardiac STAT3 and STAT3 KO mice develop heart failure with age, we tested the hypothesis that reduced STAT3 transcriptional activity contributes at an early stage to remodeling that precedes heart failure in hypertension using SA mice with a STAT3 S727A mutation. SA and wild type (WT) mice received angiotensin (A) II (1000 ng/kg/min) or saline (S) for 17 days. Hearts of WT and SA mice had similar levels of STAT3-induced protective proteins Bcl-xL and SOD2, and unlike STAT3 KO mice, cardiac miR-199a levels were not increased in SA mice. AII increased systolic blood pressure measured by telemetry in SA (124 ± 1 to 167 ± 3) and WT (122 ± 3 to 162 ± 3) mice to the same extent. AII increased cardiac levels of cytokines (pg/μg protein) associated with heart failure in both WT and SA mice, but significantly less so (P<0.05) in SA mice; IL-6, 13.6 ± 1.4 vs. 9.1 ± 0.6; TGFβ, 56 ± 4 vs. 38 ± 3 and MCP1 35 ± 2 vs. 22 ± 2. Compared to WT mice, hearts of SA mice showed signs of developing systolic dysfunction with AII as seen by a significant (P<0.05) reduction in ejection fraction (63.7 ± 7.1 to 51.7 ± 6.9) and fractional shortening (34.3 ± 4.9 to 26.4 ± 4.3). AII caused fibrosis in the left ventricle of both WT and SA mice characterized by cardiac myocyte loss and increased % collagen: WT+S, 5.59 ± 0.34; WT+AII, 15.70 ± 1.87; SA+S, 6.70 ± 0.40; SA+AII, 16.50 ± 1.91. In WT+AII mice there was a nonsignificant trend towards a loss of myofibrillar content of cardiac myocytes, but an increase in the mass of the myofibrils (IOD/myofibrillar area). In contrast, cardiac myocytes of SA+AII mice had a significant (P<0.001) % loss in myofibrils (5.71 ± 0.28) compared to SA+S (0.75 ± 0.07), WT+S (0.80 ± 0.06) and WT+AII (1.54 ± 0.10) mice. In addition, the mass of the myofibrils in SA+AII mice (6.01 ± 0.07) was significantly less (P<0.001) than those of SA+S mice (6.46 ± 0.04), although greater than WT+S (4.85 ± 0.06) or WT+AII (5.27 ± 0.08) mice. Our findings reveal that STAT3 transcriptional activity is important for proper morphology of the myofibrils of cardiac myocytes. Loss of STAT3 activity may impair cardiac function in the hypertensive heart due to defective myofibrillar structure and remodeling that may lead to heart failure.

scholarly journals What Type of Patients Did PARAGON-HF Select? Insights from a Real-World Prospective Cohort of Patients with Heart Failure and Preserved Ejection Fraction

2020 ◽  
Vol 9 (11) ◽  
pp. 3669 ◽  
Author(s):  
René Rettl ◽  
Theresa-Marie Dachs ◽  
Franz Duca ◽  
Christina Binder ◽  
Fabian Dusik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Real World ◽  
Treatment Options ◽  
National Registry ◽  
Preserved Ejection Fraction ◽  
Eligibility Criteria ◽  
Patients With Heart Failure ◽  
Long Term Prognosis

The PARAGON-HF clinical trial suggested that sacubitril/valsartan may become a treatment option for particular subgroups of patients with heart failure and preserved ejection fraction (HFpEF). However, the proportion of real-world HFpEF patients who are theoretically superimposable with the PARAGON-HF population is yet unknown. The present study was performed to define the proportion of real-world PARAGON-HF-like patients and to describe their clinical characteristics and long-term prognosis in comparison with those who would not meet PARAGON-HF criteria. We systematically applied PARAGON-HF inclusion and exclusion criteria to a total of 427 HFpEF patients who have been participating in a prospective national registry between December 2010 and December 2019. In total, only 170 (39.8%) registry patients were theoretically eligible for PARAGON-HF. Patients not meeting inclusion criteria (41.0%) were less impaired with respect to exercise capacity (median 6-min walk distance: 385 m (IQR: 300–450) versus 323 m (IQR: 240–383); p < 0.001) had lower pulmonary pressures (mean pulmonary artery pressure (mPAP): 31.2 mmHg, standard deviation (SD): ±10.2 versus 32.8 mmHg, SD: ±9.7; p < 0.001) and better outcomes (log-rank: p < 0.001) as compared to the PARAGON-like cohort. However, patients theoretically excluded from the trial (19.2%) were those with most advanced heart failure symptoms (median 6-min walk test: 252 m (IQR: 165–387); p < 0.001), highest pulmonary pressures (mPAP: 38.2 mmHg, SD: ±12.4; p < 0.001) and worst outcome (log-rank: p = 0.037). We demonstrate here that < 40% of real-world HFpEF patients meet eligibility criteria for PARAGON-HF. We conclude that despite reasons for optimism after PARAGON-HF, a large proportion of HFpEF patients will remain without meaningful treatment options.

scholarly journals Serum Positive for the Autoantibody against theβ1-Adrenoceptor from Chinese Patients with Congestive Heart Failure DecreasesIssin Mouse Cardiac Myocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Yuan-yuan Wang ◽  
Zhi-Yong Ma ◽  
Xiao-Dong Li ◽  
Jian-chun Wang ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Myocytes ◽  
Potassium Current ◽  
Inhibitory Effect ◽  
Chinese Patients ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Electrophysiological Recordings ◽  
Patients With Heart Failure ◽  
Positive Serum

Autoantibodies targeting the β1-adrenergic receptor (AAB-β1) display agonist-like effects, which may have a pathogenic role in the progression of heart failure. Here, we used the electrophysiological recordings to explore the effects of AAB-β1-positive serum from Chinese patients with heart failure on the activity of the peak transient outward potassium current (Ito) and the end 50 ms steady-state potassium current (Iss) in mouse cardiac myocytes. We found that the AAB-β1-positive serum had no effect on the activity ofIto, but it produced a decrease in the currents ofIss. A low concentration of positive serum (1/100) had a small inhibitory effect onIss. However, positive serum at 1 : 10, 1 : 20, and 1 : 50 significantly decreasedIss. The concentration-dependence analysis showed that the EC50of AAB-β1-positive serum was 1/60.24 and its nH was 2.86. It indicated that the AAB-β1could inhibitIssin mouse cardiomyocyte in a concentration-dependent manner.

Effects of functional tricuspid regurgitation on renal function and long-term prognosis in patients with heart failure

2017 ◽  
Vol 18 (2) ◽  
pp. 60-68 ◽  
Author(s):  
Eustachio Agricola ◽  
Claudia Marini ◽  
Stefano Stella ◽  
Alberto Monello ◽  
Andrea Fisicaro ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Tricuspid Regurgitation ◽  
Functional Tricuspid Regurgitation ◽  
Patients With Heart Failure ◽  
Long Term Prognosis

scholarly journals Cardiac resynchronization therapy in a patient with noncompaction of ventricular myocardium: a case report

2021 ◽  
Author(s):  
Juan Wang ◽  
Dasheng Lu ◽  
Yunong Han ◽  
Hongxiang zhang
Keyword(s):  
Heart Failure ◽  
Cardiac Resynchronization Therapy ◽  
Ventricular Myocardium ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Bundle Branch Block ◽  
Noncompaction Of Ventricular Myocardium ◽  
Patients With Heart Failure ◽  
Long Term Prognosis

Noncompaction of ventricular myocardium (NVM) is a rare and specific type of congenital cardiomyopathy that occurs in only 0.05% in adults. Cardiac resynchronization therapy (CRT) improves cardiac function and long-term prognosis in patients with heart failure with left bundle branch block, but its efficacy on NVM is uncertain

Abstract 16345: Increase in Serum Chloride Level During Hospitalization Leads to Improved Clinical Outcomes in Patients With Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shota Shirotani ◽  
Kentaro Jujo ◽  
Makoto Kishihara ◽  
Shounosuke Watanabe ◽  
Nana Endo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcomes ◽  
Primary Endpoint ◽  
Prognostic Impact ◽  
Chloride Level ◽  
Cox Regression Analysis ◽  
Serum Chloride ◽  
Patients With Heart Failure ◽  
Long Term Prognosis

Introduction: Serum chloride levels both at admission and at discharge in patients with heart failure (HF) are independently associated with the incidence of adverse clinical outcomes. However, there has been few reports focusing on the prognostic impact of the change in serum chloride level during the hospitalization on the long-term prognosis after discharge. Hypothesis: We thus hypothesized that changes in serum chloride during the hospitalization is an independent prognostic predictor after discharge in HF patients. Methods: This observational study included 1,913 consecutive patients who admitted to hospital due to worsening of HF and discharged alive in a single university hospital. After excluding patients who received regular hemodialysis, 1,762 patients were ultimately analyzed. The primary endpoint of this study was death from any cause. Result: Overall serum chloride level was significantly decreased from the admission to discharge (103 [100-106] mEq/L to 102 [99-105] mEq/L, P<0.001). During the observation period with 512 days of median follow-up, 286 patients (16.2%) died. Multivariate Cox regression analysis revealed that increase in serum chloride level during the index hospitalization was independently associated with lower rates of mortality, even after the adjustment of diverse covariates including serum chloride level at admission (hazard ratio (HR): 0.94, 95% confidence interval: 0.90-0.98). When dividing the study population into tertiles by chloride levels at admission, patients with the lower baseline chloride level had the greater reduction in HR of the primary endpoint by the increase of chloride level during the hospitalization (Figure). Conclusion: Increase in serum chloride level during hospitalization may be associated with better post-discharge prognosis in HF patients. This could be a new therapeutic target for heart failure to improve long-term prognosis.

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