Proteome Dynamics and Bioinformatics Reveal Major Alterations in the Turnover Rate of Functionally Related Cardiac and Plasma Proteins in a Dog Model of Congestive Heart Failure.
J Card Fail
; 28(4): 588-600, 2022 04.
Article
de En
| MEDLINE
| ID: mdl-34785403
ABSTRACT
Protein pool turnover is a critically important cellular homeostatic component, yet it has been little explored in the context of heart failure (HF) pathophysiology. We used in vivo 2H labeling/proteome dynamics for the nonbiased discovery of turnover alterations involving functionally linked cardiac and plasma proteins in canine tachypacing-induced HF, an established preclinical model of dilated cardiomyopathy. Compared with controls, dogs with congestive HF displayed bidirectional turnover changes of 28 cardiac proteins, that is, a reduced half-life of several key enzymes involved in glycolysis, homocysteine metabolism and glycogenesis, and increased half-life of proteins involved in proteolysis. Changes in plasma proteins were more modest only 5 proteins, involved in various functions including proteolysis inhibition, hemoglobin, calcium and ferric iron binding, displayed increased or decreased turnover rates. In other dogs undergoing cardiac tachypacing, we infused for 2 weeks the myokine Follistatin-like protein 1, known for its ameliorative effects on HF-induced alterations. Proteome dynamics proved very sensitive in detecting the partial or complete prevention, by Follistatin-like protein 1, of cardiac and plasma protein turnover alterations. In conclusion, our study unveiled, for the first time in a large mammal, numerous HF-related alterations that may serve as the basis for future mechanistic research and/or as conceptually new molecular markers.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines apparentées à la follistatine
/
Défaillance cardiaque
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Card Fail
Sujet du journal:
CARDIOLOGIA
Année:
2022
Type de document:
Article
Pays d'affiliation:
Italie