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Dilated cardiomyopathy (DCM) is among the most common cardiac diseases in dogs. Its pathogenesis is not fully understood, but myocardial remodeling and inflammation are suspected to be involved. The present study aimed to characterize the pathological processes in canine DCM, investigating morphological changes in association with the expression of relevant cytokines and remodeling markers. The myocardium of 17 dogs with DCM and 6 dogs without cardiac diseases was histologically evaluated, and selected cases were further examined by immunohistochemistry, morphometry, and reverse transcription quantitative PCR. In DCM, the myocardium exhibited subtle but statistically significant diffuse quantitative changes. These comprised increased interstitial collagen deposition and macrophage numbers, as well as an overall reduced proportion of contractile tissue. This was accompanied by a significant increase in myocardial transcription of intracellular adhesion molecule (ICAM) 1, inflammatory cytokines, and remodeling enzymes. Laser microdissection showed that cardiomyocytes transcribed most relevant markers including ICAM-1, tumor necrosis factor α, transforming growth factor β (TGF-β), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of MMP (TIMP) 1 and TIMP-2. In addition, there were multifocal cell-rich lesions characterized by fibrosis, neovascularization, macrophage infiltration, and cardiomyocyte degeneration. In these, macrophages were often found to express ICAM-1, TGF-β, and vascular endothelial growth factor; the former two were also expressed by cardiomyocytes. These results characterize the diffuse myocardial remodeling processes that occur in DCM. The observed multifocal cell-rich lesions might result from reduced tissue perfusion. Macrophages and cardiomyocytes seem to actively contribute to the remodeling processes, which ultimately lead to cardiac dilation and dysfunction. The precise role of the involved cells and the factors initiating the remodeling process still needs to be identified.
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http://dx.doi.org/10.1177/0300985820906895 | DOI Listing |
J Cell Mol Med
December 2024
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Dilated cardiomyopathy (DCM), a form of non-ischaemic myocardial disease, is characterised by structural and functional cardiac abnormalities. As defined by the World Health Organisation, DCM constitutes a significant cardiac pathology, leading to increased morbidity and mortality due to complications such as heart failure and arrhythmias. The diagnostic process for DCM predominantly employs echocardiography and MRI, with biomarkers like NT-pro BNP and troponin providing supportive, yet non-specific, evidence.
View Article and Find Full Text PDFPediatr Cardiol
December 2024
Faculty of Medicine, Alexandria University, Alexandria, Egypt.
The article "The Influence of Arrhythmia on the Outcomes of Pediatric Patients with Idiopathic Dilated Cardiomyopathy" by Mohammad Dalili et al. provides valuable insights into the impact of arrhythmia on idiopathic dilated cardiomyopathy outcomes. However, it presents with certain limitations.
View Article and Find Full Text PDFThe super-relaxed (SRX) state of myosin ATPase activity is critical for striated muscle function, and its dysregulation is linked to cardiomyopathies. It is unclear whether the SRX state exchanges readily with the disordered-relaxed (DRX) state, and whether the SRX state directly corresponds to the folded back interacting-head motif (IHM). Using recombinant β-cardiac heavy meromyosin (HMM) and subfragment 1 (S1), which cannot form the IHM, we show that the SRX and DRX populations are in rapid equilibrium, dependent on myosin head-tail interactions.
View Article and Find Full Text PDFIn cardiac muscle, many myosin molecules are in a resting or "OFF" state with their catalytic heads in a folded structure known as the interacting heads motif (IHM). Many mutations in the human β-cardiac myosin gene that cause hypertrophic cardiomyopathy (HCM) are thought to destabilize (decrease the population of) the IHM state. The effects of pathogenic mutations on the IHM structural state are often studied using indirect assays, including a single-ATP turnover assay that detects the super-relaxed (SRX) biochemical state of myosin functionally.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA. Electronic address:
The sarco(endo)plasmic reticulum Ca ATPase (SERCA) is a membrane transporter that creates and maintains intracellular Ca stores. In the heart, SERCA is regulated by an inhibitory interaction with the monomeric form of the transmembrane micropeptide phospholamban (PLB). PLB also forms avid homo-pentamers, and dynamic exchange of PLB between pentamers and SERCA is an important determinant of cardiac responsiveness to exercise.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!