Search results for "MYOPATHY"

Gene Expression Analyses during Spontaneous Reversal of Cardiomyopathy in Mice with Repressed Nuclear CUG-BP, Elav-Like Family (CELF) Activity in Hea…

2015

CUG-BP, Elav-like family (CELF) proteins regulate cell type- and developmental stage-specific alternative splicing in the heart. Repression of CELF-mediated splicing activity via expression of a nuclear dominant negative CELF protein in heart muscle was previously shown to induce dysregulation of alternative splicing, cardiac dysfunction, cardiac hypertrophy, and dilated cardiomyopathy in MHC-CELFΔ transgenic mice. A “mild” line of MHC-CELFΔ mice that expresses a lower level of the dominant negative protein exhibits cardiac dysfunction and myopathy at a young age, but spontaneously recovers normal cardiac function and heart size with age despite the persistence of splicing defects. To the b…

Bone marrow mononuclear cell separation yield in myocardium infarction, coronary disease and type 2 diabetes and dilated cardiomyopathy patient groups

2013

Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

2021

Abstract Aims  Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results  We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identif…

Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardioto…

2015

Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal model…

Evaluation of ventricular wall stress and cardiac function in patients with dilated cardiomyopathy

2015

Dilated cardiomyopathy is a heart disease characterized by both left ventricular dilatation and left ventricular systolic dysfunction, leading to cardiac remodeling and ultimately heart failure. We aimed to investigate the effect of dilated cardiomyopathy on the pump performance and myocardial wall mechanics using patient-specific finite element analysis. Results evinced pronounced end-systolic wall stress on left ventricular wall of patients with dilated cardiomyopathy as compared to that of normal hearts. In dilated cardiomyopathy, both end-diastolic and end-systolic pressure–volume relationships of left ventricle and right ventricle were shifted to the right compared to controls, sugges…

Recombinant growth hormone therapy in patients with ischemic cardiomyopathy : effects on hemodynamics, left ventricular function, and cardiopulmonary…

1999

Background —We studied the effects of recombinant growth hormone (rhGH) on exercise capacity and cardiac function in patients with ischemic cardiomyopathy. Methods and Results —Seven patients (aged 55±9 years) with mild to moderate congestive heart failure (ejection fraction 31±4%) who were on standard therapy were included. The patients were studied at baseline, after 3 months of rhGH treatment, and 3 months after rhGH discontinuation. Cardiac function was assessed by exercise capacity, right heart catheterization at rest and after submaximal exercise, MRI, echocardiography, and Holter monitoring. When administered at a dose of 2 IU/d, rhGH doubled the serum concentration of insulin-like …

Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity

2007

Background and aim: The clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. The role of the individual genetic makeup in this disorder is poorly understood. Alterations in genes encoding cardiac cytoskeleton or sarcolemma proteins may increase the susceptibility to doxorubicin-related cardiotoxicity. Methods: Female dystrophin-deficient mice (MDX) and age-matched wild-type mice underwent chronic treatment with doxorubicin. Cardiac function and tissue damage were assessed by echocardiography and histopathology, respectively. Gene expression changes were investigated using microarrays. Results: DOX treat…

Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure

2008

AIMS: Recent studies have demonstrated the importance of chromatin remodelling via histone acetylation/deacetylation for the control of cardiac gene expression. Specific histone deacetylases (HDACs) can, in fact, play a positive or negative role in determining cardiac myocyte (CM) size. Here, we report on the effect on hypertrophy development of three inhibitors (HDACi) of class I HDACs. METHODS AND RESULTS: The compounds were first analysed in vitro by scoring hypertrophy, expression of foetal genes, and apoptosis of neonatal rat CMs stimulated with phenylephrine, an alpha1-adrenergic agonist. This initial screening indicated that a truncated derivative of apicidin with class I HDAC specif…

Destination Therapy with Left Ventricular Assist Devices in Non-transplant Centres: The Time is Right

2020

For almost half a century, cardiac transplant has been the only long-term treatment for patients with end-stage heart failure. Implantable left ventricular assist devices (LVADs) have emerged as a new treatment option for advanced heart failure as destination therapy for patients either too old or not suitable for transplant. A meta-analysis presenting head-to-head comparisons of cardiac transplant versus LVAD as destination therapy (LVAD-DT) found no difference in 1-year mortality rates between LVAD-DT and cardiac transplant (OR 1.49; 95% CI [0.48–4.66]; I2=82.8%). Moreover, a recent subanalysis from the Interagency Registry for Mechanically Assisted Circulatory Support found similar outco…

Impact of intra-aortic balloon counterpulsation on all-cause mortality among patients with Takotsubo syndrome complicated by cardiogenic shock: resul…

2023

Abstract Aims Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction and can be complicated by cardiogenic shock (CS). However, few data are available on optimal care in TTS complicated by CS. Aim of this study was to evaluate short- and long-term impact of intra-aortic balloon pumping (IABP) on mortality in this setting. Methods and results In a multi-centre, international registry on TTS, 2248 consecutive patients were enrolled from 38 centres from Germany, Italy, and Spain. Of the 2248 patients, 212 (9.4%) experienced CS. Patients with CS had a higher prevalence of diabetes (27% vs. 19%), male sex (25% vs. 10%), and right ventricular involvement (10% vs. 5%) (P …