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Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.
J Clin Invest
January 2025
Department of Biomedical Engineering, Columbia University, New York, New York, USA.
Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).
View Article and Find Full Text PDFFour cardiomyopathy patients with a heterozygous DSG2 p.Arg119Ter variant.
Hum Genome Var
December 2024
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
DSG2, encoding desmoglein-2, is one of the causative genes of arrhythmogenic cardiomyopathy. We previously identified a homozygous DSG2 p.Arg119Ter stop-gain variant in a patient with juvenile-onset cardiomyopathy and advanced biventricular heart failure.
View Article and Find Full Text PDF2'-Hydroxycinnamaldehyde, a Natural Product from Cinnamon, Alleviates Ischemia/Reperfusion-Induced Microvascular Dysfunction and Oxidative Damage in Rats by Upregulating Cytosolic BAG3 and Nrf2/HO-1.
Int J Mol Sci
December 2024
School of Life Science, National Taiwan Normal University, Taipei 117, Taiwan.
2'-Hydroxycinnamaldehyde (HCA), a natural product isolated from the bark of , has anti-inflammatory and anti-tumor activities. In this study, we explored whether HCA preconditioning could protect the heart against ischemia/reperfusion (I/R)-induced oxidative injury through cytosolic Bcl-2-associated athanogene 3 (BAG3) upregulation. In vivo HCA preconditioning was performed intraperitoneally in adult male Wistar rats (50 mg/kg body weight) three times/week for 2 weeks before cardiac I/R injury.
View Article and Find Full Text PDFBidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3.
JAMA Cardiol
December 2024
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Article Synopsis
- The study investigates the role of BAG3 genetic variants in heritable dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), focusing on how these variants contribute to the variability in disease expression and severity.
- Conducted at the University of Pennsylvania Health System, the research included a large cohort of patients, using whole-exome sequencing linked to electronic health records to analyze associations between BAG3 variants and clinical traits.
- Results indicated that the common C151R BAG3 variant is linked to a lower risk of DCM but an increased risk of HCM, with carriers showing better long-term health outcomes compared to noncarriers.
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