In vivo elongation of thin filaments results in heart failure


Autoři: Lei Mi-Mi aff001;  Gerrie P. Farman aff001;  Rachel M. Mayfield aff001;  Joshua Strom aff001;  Miensheng Chu aff001;  Christopher T. Pappas aff001;  Carol C. Gregorio aff001
Působiště autorů: Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ, United States of America aff001
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0226138

Souhrn

A novel cardiac-specific transgenic mouse model was generated to identify the physiological consequences of elongated thin filaments during post-natal development in the heart. Remarkably, increasing the expression levels in vivo of just one sarcomeric protein, Lmod2, results in ~10% longer thin filaments (up to 26% longer in some individual sarcomeres) that produce up to 50% less contractile force. Increasing the levels of Lmod2 in vivo (Lmod2-TG) also allows us to probe the contribution of Lmod2 in the progression of cardiac myopathy because Lmod2-TG mice present with a unique cardiomyopathy involving enlarged atrial and ventricular lumens, increased heart mass, disorganized myofibrils and eventually, heart failure. Turning off of Lmod2 transgene expression at postnatal day 3 successfully prevents thin filament elongation, as well as gross morphological and functional disease progression. We show here that Lmod2 has an essential role in regulating cardiac contractile force and function.

Klíčová slova:

Cardiac muscles – Fibrosis – Hyperexpression techniques – Mouse models – Muscle contraction – Cardiomyocytes – Heart – Sarcomeres


Zdroje

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