MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations.

Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a "malignant" phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy.

The Effect of TNF Inhibitors on Cardiovascular Events in Psoriasis and Psoriatic Arthritis: an Updated Meta-Analysis.

TNF inhibitors have been used in psoriasis (Pso) and psoriatic arthritis (PsA), which were associated with increased risk of cardiac and cerebrovascular events. However, whether TNF inhibitors reduce cardiovascular event is still unclear. Therefore, we aimed to evaluate the effect of TNF inhibitors on adverse cardiovascular events (CVEs) in Pso with or without PsA. We undertook a meta-analysis of clinical trials identified in systematic searches of MEDLINE, EMBASE, Wanfang database, Cochrane Database, and Google scholar through December 31, 2015. Five studies (49,795 patients) were included. Overall, compared with topical/photo treatment, TNF inhibitors were associated with a significant lower risk of CVE (RR, 0.58; 95 % CI, 0.43 to 0.77; P < 0.001; I (2) = 66.2 %). Additionally, compared with methotrexate (MTX) treatment, risk of CVE was also markedly decreased in the TNF inhibitor group (RR, 0.67; 95 % CI, 0.52 to 0.88; P = 0.003; I (2) = 9.3 %). Meanwhile, TNF inhibitors were linked to reduced incidence of myocardial infarction compared with topical/photo or MTX treatment (RR, 0.73; 95 % CI, 0.59 to 0.90; P = 0.003; I (2) = 56.2 % and RR, 0.65; 95 % CI, 0.48 to 0.89; P = 0.007; I (2) = 0.0 %, respectively). Furthermore, there was a trend of decreased rate of mortality in the TNF inhibitor group compared with other therapy (RR, 0.90; 95 % CI, 0.54 to 1.50; P = 0.68; I (2) = 70.9 %). TNF inhibitors appear to have net clinical benefits with regard to adverse cardiovascular events in Pso and/or PsA. Rigorous randomized controlled trials will need to evaluate whether TNF inhibitors truly result in reduction of cardiovascular diseases.