Cardiac Myosin Binding Protein-C Phosphorylation Mitigates Age-Related Cardiac Dysfunction
| Autor: | Jerome P. Trzeciakowski, R. John Solaro, Paola C Rosas, Heidi A. Creed, Chad M. Warren, Carl W. Tong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cardiac function curve lcsh:Diseases of the circulatory (Cardiovascular) system medicine.medical_specialty Diastole heart failure HFpEF heart failure with preserved ejection fraction macromolecular substances cMyBP-C cardiac myosin binding protein-C 030204 cardiovascular system & hematology HF heart failure cTnI cardiac troponin I Muscle hypertrophy Cardiac dysfunction 3SA mutated 3 serines to 3 alanines to mimic hypophosphorylated cardiac myosin binding protein-C (S273A S282A and S302A) HOP hydroxyproline 03 medical and health sciences PRECLINICAL RESEARCH 0302 clinical medicine Internal medicine medicine EF ejection fraction Papillary muscle LV left ventricular ANOVA analysis of variance cardiac myosin binding protein-C business.industry dyastolic dysfunction phosphorylation Binding protein aging 3SD mutated 3 serines to 3 aspartic acids to mimic phosphorylated cMyBP-C (S273D S282D and S302D) medicine.disease 030104 developmental biology medicine.anatomical_structure Endocrinology lcsh:RC666-701 Heart failure Phosphorylation Cardiology and Cardiovascular Medicine business |
| Zdroj: | JACC: Basic to Translational Science JACC: Basic to Translational Science, Vol 4, Iss 7, Pp 817-830 (2019) |
| ISSN: | 2452-302X |
| Popis: | Visual Abstract Highlights • With aging, phosphorylated-mimetic cMyBP-C mice exhibited better survival, better preservation of systolic and diastolic functions, and unchanging wall thickness compared with control mice. • Aged wild-type equivalent mice exhibited decreasing cMyBP-C phosphorylation (S273 and S282) along with worsening cardiac function and hypertrophy similarly to what was observed in hypophosphorylated cMyBP-C mice. • Intact papillary muscle experiments suggest that cMyBP-C phosphorylation increased cross-bridge detachment rates as the underlying mechanism. • Phosphorylating cMyBP-C is therefore a novel mechanism that can prevent aging-related development of cardiac dysfunction. Summary Cardiac myosin binding protein-C (cMyBP-C) phosphorylation prevents aging-related cardiac dysfunction. We tested this hypothesis by aging genetic mouse models of hypophosphorylated cMyBP-C, wild-type equivalent, and phosphorylated-mimetic cMyBP-C for 18 to 20 months. Phosphorylated-mimetic cMyBP-C mice exhibited better survival, better preservation of systolic and diastolic functions, and unchanging wall thickness. Wild-type equivalent mice showed decreasing cMyBP-C phosphorylation along with worsening cardiac function and hypertrophy approaching those found in hypophosphorylated cMyBP-C mice. Intact papillary muscle experiments suggested that cMyBP-C phosphorylation increased cross-bridge detachment rates as the underlying mechanism. Thus, phosphorylating cMyBP-C is a novel mechanism with potential to treat aging-related cardiac dysfunction. |
| Databáze: | OpenAIRE |
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