Lumican accumulates with fibrillar collagen in fibrosis in hypertrophic cardiomyopathy

Aims Familial hypertrophic cardiomyopathy (HCM) is the most common form of inherited cardiac disease. It is characterized by myocardial hypertrophy and diastolic dysfunction, and can lead to severe heart failure, arrhythmias, and sudden cardiac death. Cardiac fibrosis, defined by excessive accumulat...

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Veröffentlicht in:ESC Heart Failure 2023-04, Vol.10 (2), p.858-871
Hauptverfasser: Rixon, Chloe, Andreassen, Kristine, Shen, Xin, Erusappan, Pugazendhi Murugan, Almaas, Vibeke Marie, Palmero, Sheryl, Dahl, Christen Peder, Ueland, Thor, Sjaastad, Ivar, Louch, William Edward, Stokke, Mathis Korseberg, Tønnessen, Theis, Christensen, Geir, Lunde, Ida Gjervold
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Sprache:eng
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Zusammenfassung:Aims Familial hypertrophic cardiomyopathy (HCM) is the most common form of inherited cardiac disease. It is characterized by myocardial hypertrophy and diastolic dysfunction, and can lead to severe heart failure, arrhythmias, and sudden cardiac death. Cardiac fibrosis, defined by excessive accumulation of extracellular matrix (ECM) components, is central to the pathophysiology of HCM. The ECM proteoglycan lumican is increased during heart failure and cardiac fibrosis, including HCM, yet its role in HCM remains unknown. We provide an in‐depth assessment of lumican in clinical and experimental HCM. Methods Left ventricular (LV) myectomy specimens were collected from patients with hypertrophic obstructive cardiomyopathy (n = 15), and controls from hearts deemed unsuitable for transplantation (n = 8). Hearts were harvested from a mouse model of HCM; Myh6 R403Q mice administered cyclosporine A and wild‐type littermates (n = 8–10). LV tissues were analysed for mRNA and protein expression. Patient myectomy or mouse mid‐ventricular sections were imaged using confocal microscopy, direct stochastic optical reconstruction microscopy (dSTORM), or electron microscopy. Human foetal cardiac fibroblasts (hfCFBs) were treated with recombinant human lumican (n = 3) and examined using confocal microscopy. Results Lumican mRNA was increased threefold in HCM patients (P 
ISSN:2055-5822
2055-5822
DOI:10.1002/ehf2.14234