Mutation or altered expression of ICD proteins results in various cardiac diseases, such as ARVC (arrhythmogenic right ventricular cardiomyopathy), dilated cardiomyopathy, and hypotrophy cardiomyopathy, eventually leading to heart failure.
Severe Cardiac Dysfunction and Death Caused by Arrhythmogenic Right Ventricular Cardiomyopathy Type 5 Are Improved by Inhibition of Glycogen Synthase Kinase-3β.
The genetic test was positive in 12 (26%; 95% CI 15.6-40.3) patients; 10 (21.7%) had PKP2 mutation related to arrhythmogenic right ventricular dysplasia mutation, one (2.2%) KCNQ1 mutation and one (2.2%) SCN5A mutation related to channelopathies.
Blockade of the renin-angiotensin-aldosterone system in patients with arrhythmogenic right ventricular dysplasia: A double-blind, multicenter, prospective, randomized, genotype-driven study (BRAVE study).
A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease.
Plasma levels of miR-144-3p, 145-5p, 185-5p, and 494 were significantly elevated in definite ARVC patients with VA. An increased plasma level of miR-494 was associated with the recurrence of VA after ablation in definite ARVC patients.
Nor did we find a difference in the prevalence of rare PLEC variants in ARVC patients with or without a desmosomal likely pathogenic/pathogenic variant (14% versus 8%, respectively).
Then the ARVC-related four key biological pathways (cytokine-cytokine receptor interaction, chemokine signaling pathway, neuroactive ligand receptor interaction, and JAK-STAT signaling pathway) and four hub genes (<i>CXCL2, TNFRSF11B, LIFR</i>, and <i>C5AR1</i>) in ARVC samples were further identified by GSNCA method.
Additional rare TJP1 variants have been identified in 1 of 40 Italian probands (c.793C>T p.(R265W)) with arrhythmogenic right ventricular cardiomyopathy and in 2 of 43 Dutch/German patients (c. 986C>T, p.(S329L) and c.1079A>T, p.(D360V)) with dilated cardiomyopathy and recurrent ventricular tachycardia.
One hundred and thirty-seven (137) individuals meeting 2010 TFC for a diagnosis of ARVC, negative for pathogenic desmosomal variants, TMEM43, SCN5A, and PLN were screened for variants in the sarcomere genes (ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNC1, TNNI3, TNNT2, and TPM1) through either clinical or research genetic testing.
Then the ARVC-related four key biological pathways (cytokine-cytokine receptor interaction, chemokine signaling pathway, neuroactive ligand receptor interaction, and JAK-STAT signaling pathway) and four hub genes (<i>CXCL2, TNFRSF11B, LIFR</i>, and <i>C5AR1</i>) in ARVC samples were further identified by GSNCA method.
Our most significant discovery was the lipid metabolism reprogramming of both ARVC ventricles in accordance with the upregulation of lipogenesis factors such as FABP4 and FASN.
In a manner similar to that of the well-defined DCM heart failure model, the ARVC model demonstrates the downregulation of mitochondrial function proteins and the effects of many heart failure regulators such as TGFB, RICTOR, and KDM5A.
This comprehensive proteogenomics profiling study reveals that an activation of C/EBPα, along with the upregulation of its lipogenesis targets, accounts for lipid storage and acts as a hallmark of ARVC.
Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified.
Our most significant discovery was the lipid metabolism reprogramming of both ARVC ventricles in accordance with the upregulation of lipogenesis factors such as FABP4 and FASN.
Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRβ protein is absent from the nucleus of cardiomyocytes from patients with DCM but not other forms of cardiomyopathy (ischemic, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy).
In particular, we detected three variants in OBSCN gene in ARVC patients, four variants in ANK2 gene and two variants in DLG1, TRPM4, and AKAP9 genes in DCM patients, two variants in PSEN2 gene and four variants in AKAP9 gene in HCM patients.
It confirmed the involvement of HCN4 mutations in the combined bradycardia–myocardial non-compaction phenotype, and also suggested, for the first time, the involvement of PKP2, usually associated with arrhythmogenic right ventricular dysplasia, in ventricular non-compaction.