The molecular mechanisms that drive the development of cardiac hypertrophy in hypertrophic cardiomyopathy (HCM) remain elusive. Accumulated evidence suggests that microRNAs are essential regulators of cardiac remodelling. We have been suggested that microRNAs could play a role in the process of HCM. To uncover which microRNAs were changed in their expression, microRNA microarrays were performed on heart tissue from HCM patients (n = 7) and from healthy donors (n = 5). Among the 13 microRNAs that were differentially expressed in HCM, miR-451 was the most down-regulated. Ectopic overexpression of miR-451 in neonatal rat cardiomyocytes (NRCM) decreased the cell size, whereas knockdown of endogenous miR-451 increased the cell surface area. Luciferase reporter assay analyses demonstrated that tuberous sclerosis complex 1 (TSC1) was a direct target of miR-451. Overexpression of miR-451 in both HeLa cells and NRCM suppressed the expression of TSC1. Furthermore, TSC1 was significantly up-regulated in HCM myocardia, which correlated with the decreased levels of miR-451. As TSC1 is a known positive regulator of autophagy, we examined the role of miR-451 in the regulation of autophagy. Overexpression of miR-451 in vitro inhibited the formation of the autophagosome. Conversely, miR-451 knockdown accelerated autophagosome formation. Consistently, an increased number of autophagosomes was observed in HCM myocardia, accompanied by up-regulated autophagy markers, and the lipidated form of LC3 and Beclin-1. Taken together, our findings indicate that miR-451 regulates cardiac hypertrophy and cardiac autophagy by targeting TSC1. The down-regulation of miR-451 may contribute to the development of HCM and may be a potential therapeutic target for this disease.

Cardiac hypertrophy has been known as an independent predictor for cardiovascular morbidity and mortality. Molecular mechanisms underlying the development of heart failure remain elusive. Recently, microRNAs (miRs) have been established as important regulators in cardiac hypertrophy. Here, we reported miR-221 was up-regulated in both transverse aortic constricted mice and patients with hypertrophic cardiomyopathy (HCM). Forced expression of miR-221 by transfection of miR-221 mimics increased myocyte cell size and induced the re-expression of fetal genes, which were inhibited by the knockdown of endogenous miR-221 in cardiomyocytes. The TargetScan algorithm-based prediction identified that p27, a cardiac hypertrophic suppressor, is the putative target of miR-221, which was confirmed by luciferase assay and Western blotting. In conclusion, our results demonstrated that miR-221 regulated cardiomyocyte hypertrophy probably through down-regulation of p27, suggesting that miR-221 may be a new intervention target for cardiac hypertrophy.

Anomalous muscle bundles are common in hypertrophic obstructive cardiomyopathy, and they may lead to middle-apical obstruction. Surgical myectomy provides excellent clinical outcomes with low risk for sufficient relief of obstruction and radical correction of intraventricular anomalies in patients with hypertrophic obstructive cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) represents one of the most common heritable heart diseases. However, the signalling pathways and regulatory networks underlying the pathogenesis of HCM remain largely unknown. Here, we present a strand-specific RNA-seq dataset for both coding and lncRNA profiling in myocardial tissues from 28 HCM patients and 9 healthy donors. This dataset constitutes a valuable resource for the community to examine the dysregulated coding and lncRNA genes in HCM versus normal conditions.

OBJECTIVESThe aim was to assess the early and mid-term clinical effects of transaortic extended septal myectomy (TAESM) on obstructive hypertrophic cardiomyopathy (HCM) in China.METHODSNinety-three consecutive patients [57 men; mean age 45.8 ± 13.4 (11–74) years] with obstructive HCM underwent TAESM in Fuwai hospital. Their clinical data were analysed retrospectively. All the patients had drug-refractory symptoms and left ventricular outflow tract (LVOT) obstruction with a resting or physically provoked gradient of ≥50 mmHg. Preoperative transthoracic, intra-operative transoesophageal and postoperative transthoracic echocardiography was performed to assess LVOT gradients, septal thickness, LVOT diameter, mitral valve function, etc. Systolic anterior motion (SAM) of the anterior mitral valve leaflet had been detected in all preoperatively.RESULTSAll the surgical procedures of the 93 patients were technically successful. The average length of postoperative stay was 7.8 ± 3.7 days. The 30-day and in-hospital mortality was 0%. Initial postoperative transoesophageal echocardiography (TEE) demonstrated marked reduction in LVOT gradient (91.76 ± 25.08 to 14.34 ± 13.44 mmHg, P < 0.0005) and significant improvement in mitral regurgitation (MR; P < 0.0005). Concomitant surgical procedures were carried out in 37 (39.8%). Complete atrioventricular block occurred in 3, complete left bundle branch block in 44, intraventricular conduction delay in 18, complete right bundle branch block in 2, transient renal dysfunction in 2 and transient intra-aortic-balloon-pumping was needed in 2. No other complications were observed during hospital stay. During a follow-up of 10.72 ± 11.02 (1–24) months, there were no readmissions or deaths, and all patients subjectively reported an obvious decrease in limiting symptoms and a significant increase in physical ability. At the latest follow-up, the New York Heart Association functional class decreased from 3.09 ± 0.60 (2–4) preoperatively to 1.12 ± 0.32 (1–2) (P < 0.0005); the LVOT gradient remained low at 14.78 ± 14.01 mmHg; MR remained absent (51) or at mild-(41)-to-moderate-(1) levels and SAM resolved completely in 98.9% (92 of 93) patients.CONCLUSIONSTAESM provides excellent relief from LVOT obstruction in HCM patients, with a conspicuous clinical and echocardiographic outcome at early and mid-term follow-up. For obstructive HCM and cardiac comorbidities, concomitant cardiac procedures with TAESM can be performed with low risk and satisfactory results.