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

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

Khatia Gabisonia

Gia Burjanadze

Felix Woitek

Ayse Keles

Mitsuru Seki

Nikoloz Gorgodze

Lucia Carlucci

Serguei Ilchenko

Clara Kurishima

Kenneth Walsh

Helen Piontkivska

Fabio A Recchia

Takhar Kasumov

2022

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.

J Card Fail
. 2022 Apr;28(4):588-600. doi: 10.1016/j.cardfail.2021.11.011. Epub 2021 Nov 14.

English

https://doi.org/10.1016/j.cardfail.2021.11.011