Genotype-Dependent and -Independent Calcium Signaling Dysregulation in Human Hypertrophic Cardiomyopathy

BACKGROUND:Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS:We analyzed gene expression, protein levels, and functional assays for calcium regulat...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2016-11, Vol.134 (22), p.1738-1748
Main Authors: Helms, Adam S, Alvarado, Francisco J, Yob, Jaime, Tang, Vi T, Pagani, Francis, Russell, Mark W, Valdivia, Héctor H, Day, Sharlene M
Format: Article
Language:English
Subjects:
Calcium Signaling - genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Cardiomyopathy, Hypertrophic - genetics
Cardiomyopathy, Hypertrophic - metabolism
Carrier Proteins - biosynthesis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Case-Control Studies
Down-Regulation
Gene Expression
Genotype
Humans
RNA, Messenger - genetics
RNA, Messenger - metabolism
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
Sarcomeres - genetics
Sarcomeres - metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases - biosynthesis
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
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Summary:BACKGROUND:Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS:We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS:Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls. CaMKII protein abundance was increased only in sarcomere-mutation HCM (P
ISSN:0009-7322
1524-4539
DOI:10.1161/CIRCULATIONAHA.115.020086