Protein expression profiles in murine ventricles modeling catecholaminergic polymorphic ventricular tachycardia: effects of genotype and sex.
Ann N Y Acad Sci
; 1478(1): 63-74, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32713021
ABSTRACT
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with mutations in the cardiac ryanodine receptor (RyR2). These result in stress-induced ventricular arrhythmic episodes, with clinical symptoms and prognosis reported more severe in male than female patients. Murine homozygotic RyR2-P2328S (RyR2S/S ) hearts replicate the proarrhythmic CPVT phenotype of abnormal sarcoplasmic reticular Ca2+ leak and disrupted Ca2+ homeostasis. In addition, RyR2S/S hearts show decreased myocardial action potential conduction velocities (CV), all features implicated in arrhythmic trigger and substrate. The present studies explored for independent and interacting effects of RyR2S/S genotype and sex on expression levels of molecular determinants of Ca2+ homeostasis (CASQ2, FKBP12, SERCA2a, NCX1, and CaV 1.2) and CV (NaV 1.5, Connexin (Cx)-43, phosphorylated-Cx43, and TGF-ß1) in mice. Expression levels of Ca2+ homeostasis proteins were not altered, hence implicating abnormal RyR2 function alone in disrupted cytosolic Ca2+ homeostasis. Furthermore, altered NaV 1.5, phosphorylated Cx43, and TGF-ß1 expression were not implicated in the development of slowed CV. By contrast, decreased Cx43 expression correlated with slowed CV, in female, but not male, RyR2S/S mice. The CV changes may reflect acute actions of the increased cytosolic Ca2+ on NaV 1.5 and Cx43 function.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tachycardia, Ventricular
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Connexin 43
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Ryanodine Receptor Calcium Release Channel
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NAV1.5 Voltage-Gated Sodium Channel
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
/
Male
Language:
En
Journal:
Ann N Y Acad Sci
Year:
2020
Document type:
Article
Affiliation country:
Reino Unido