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Myosins and MyomiR Network in Patients with Obstructive Hypertrophic Cardiomyopathy
- Source :
- Biomedicines; Volume 10; Issue 9; Pages: 2180
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls). A subset of tissue-abundant myectomy samples from HCM (n = 10) and controls (n = 6) was submitted to laser-capture microdissection to isolate cardiomyocytes. We investigated the relationship among clinical phenotype, cardiac myosin proteins (MyHC6, MyHC7, and MyHC7b) measured by optimized label-free mass spectrometry, the relative genes (MYH7, MYH7B and MYLC2), and the MyomiR network (myosin-encoded microRNA (miRs) and long-noncoding RNAs (Mhrt)) measured using RNA sequencing and RT-qPCR. MyHC6 was lower in HCM vs. controls, whilst MyHC7, MyHC7b, and MyLC2 were comparable. MYH7, MYH7B, and MYLC2 were higher in HCM whilst MYH6, miR-208a, miR-208b, miR-499 were comparable in HCM and controls. These results are compatible with defective transcription by active genes in HCM. Mhrt and two miR-499-target genes, SOX6 and PTBP3, were upregulated in HCM. The presence of HCM-associated mutations correlated with PTBP3 in myectomies and with SOX6 in cardiomyocytes. Additionally, iPSC-derived cardiomyocytes, transiently transfected with either miR-208a or miR-499, demonstrated a time-dependent relationship between MyomiRs and myosin genes. The transfection end-stage pattern was at least in part similar to findings in HCM myectomies. These data support uncoupling between myosin protein/genes and a modulatory role for the myosin/MyomiR network in the HCM myocardium, possibly contributing to phenotypic diversity and providing putative therapeutic targets.
- Subjects :
- Polypyrimidine Tract Binding Protein 3 (PTBP3)
microRNA (miRs)
MyomiR (myosin-encoded miRs)
hypertrophic cardiomyopathy (HCM)
cardiomyocytes
myosin heavy chain (isoform: MyHC, gene: MYH)
miR-499
SRY-Box Transcription Factor 6 (SOX6)
Medicine (miscellaneous)
myosin heavy chain (isoform: MyHC
General Biochemistry, Genetics and Molecular Biology
gene: MYH)
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Database :
- OpenAIRE
- Journal :
- Biomedicines; Volume 10; Issue 9; Pages: 2180
- Accession number :
- edsair.doi.dedup.....c1ab7c1a7bde6700751c11f265940932
- Full Text :
- https://doi.org/10.3390/biomedicines10092180