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Extracellular Matrix From Hypertrophic Myocardium Provokes Impaired Twitch Dynamics in Healthy Cardiomyocytes.
Sewanan, Lorenzo R; Schwan, Jonas; Kluger, Jonathan; Park, Jinkyu; Jacoby, Daniel L; Qyang, Yibing; Campbell, Stuart G.
Afiliação
  • Sewanan LR; Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
  • Schwan J; Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
  • Kluger J; Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
  • Park J; Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
  • Jacoby DL; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
  • Qyang Y; Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
  • Campbell SG; Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
JACC Basic Transl Sci ; 4(4): 495-505, 2019 Aug.
Article em En | MEDLINE | ID: mdl-31468004
Hypertrophic cardiomyopathy (HCM) is often caused by single sarcomeric gene mutations that affect muscle contraction. Pharmacological correction of mutation effects prevents but does not reverse disease in mouse models. Suspecting that diseased extracellular matrix is to blame, we obtained myocardium from a miniature swine model of HCM, decellularized thin slices of the tissue, and re-seeded them with healthy human induced pluripotent stem cell-derived cardiomyocytes. Compared with cardiomyocytes grown on healthy extracellular matrix, those grown on the diseased matrix exhibited prolonged contractions and poor relaxation. This outcome suggests that extracellular matrix abnormalities must be addressed in therapies targeting established HCM.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: JACC Basic Transl Sci Ano de publicação: 2019 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: JACC Basic Transl Sci Ano de publicação: 2019 Tipo de documento: Article País de publicação: Estados Unidos