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Investigations into the Sarcomeric Protein and Ca2+-Regulation Abnormalities Underlying Hypertrophic Cardiomyopathy in Cats (Felix catus).

Messer, A E; Chan, J; Daley, A; Copeland, O; Marston, S B; Connolly, D J

Authors

A E Messer

J Chan

A Daley

O Copeland

S B Marston

D J Connolly



Abstract

Hypertrophic cardiomyopathy (HCM) is the most common single gene inherited cardiomyopathy. In cats (Felix catus) HCM is even more prevalent and affects 16% of the outbred population and up to 26% in pedigree breeds such as Maine Coon and Ragdoll. Homozygous MYBPC3 mutations have been identified in these breeds but the mutations in other cats are unknown. At the clinical and physiological level feline HCM is closely analogous to human HCM but little is known about the primary causative mechanism. Most identified HCM causing mutations are in the genes coding for proteins of the sarcomere. We therefore investigated contractile and regulatory proteins in left ventricular tissue from 25 cats, 18 diagnosed with HCM, including a Ragdoll cat with a homozygous MYBPC3 R820W, and 7 non-HCM cats in comparison with human HCM (from septal myectomy) and donor heart tissue. Myofibrillar protein expression was normal except that we observed 20–44% MyBP-C haploinsufficiency in 5 of the HCM cats. Troponin extracted from 8 HCM and 5 non-HCM cat hearts was incorporated into thin filaments and studied by in vitro motility assay. All HCM cat hearts had a higher (2.06 ± 0.13 fold) Ca2+-sensitivity than non-HCM cats and, in all the HCM cats, Ca2+-sensitivity was not modulated by troponin I phosphorylation. We were able to restore modulation of Ca2+-sensitivity by replacing troponin T with wild-type protein or by adding 100 μM Epigallocatechin 3-gallate (EGCG). These fundamental regulatory characteristics closely mimic those seen in human HCM indicating a common molecular mechanism that is independent of the causative mutation. Thus, the HCM cat is a potentially useful large animal model.

Citation

Messer, A. E., Chan, J., Daley, A., Copeland, O., Marston, S. B., & Connolly, D. J. (2017). Investigations into the Sarcomeric Protein and Ca2+-Regulation Abnormalities Underlying Hypertrophic Cardiomyopathy in Cats (Felix catus). Frontiers in Physiology, 8, 348. https://doi.org/10.3389/fphys.2017.00348

Journal Article Type Article
Acceptance Date May 12, 2017
Publication Date Jun 8, 2017
Deposit Date Jul 13, 2018
Publicly Available Date Mar 29, 2024
Journal Frontiers in Physiology
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 8
Pages 348
DOI https://doi.org/10.3389/fphys.2017.00348
Public URL https://rvc-repository.worktribe.com/output/1391614

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