Myeloid differentiation 1 (MD-1), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. Previous studies showed that MD-1 may be restricted in the immune system. In this study, we demonstrated for the first time that MD-1 was highly expressed in both human and animal hearts. We also discovered that cardiac-specific overexpression of MD-1 significantly attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of MD-1 had the opposite effects. Similar results were observed for in vitro angiotensin II-induced neonatal rat cardiomyocyte hypertrophy. The antihypertrophic effects of MD-1 under hypertrophic stimuli were associated with the blockage of MEK-ERK 1/2 and NF-κB signalling. Blocking MEK-ERK 1/2 signalling with a pharmacological inhibitor (U0126) greatly attenuated the detrimental effects observed in MD-1 knockout cardiomyocytes exposed to angiotensin II stimuli. Similar results were observed by blocking NF-κB signalling with a pharmacological inhibitor (BAY11–7082). Our data indicate that MD-1 inhibits cardiac hypertrophy and suppresses cardiac dysfunction during the remodelling process, which is dependent on its modulation of the MEK-ERK 1/2 and NF-κB signalling pathways. Thus, MD-1 might be a novel target for the treatment of pathological cardiac hypertrophy.

A b s t r a c t Background:The recurrence rate of atrial fibrillation (AF) after cryoballoon ablation in drug refractory AF patients is high. Late-recurrence of AF has various predictors. Aim:The aim of the study was to explore the related risk factors that can effectively predict late AF recurrence after cryoballoon-based pulmonary vein isolation. Methods:The PubMed and Web of Science databases were searched from 1 January 2013 to 1 August 2016, and studies were chosen that met the pre-stated inclusion criteria. The reference lists of the retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies. The strength of the relationship between different risk factors and late recurrence was assessed by the adjusted hazard ratio.Results: A total of 16 papers met the inclusion criteria and were included in the meta-analysis. The hazard ratio of late atrial arrhythmia recurrence in patients with early recurrence was 4.19 compared with the reference group (95% CI 2.73-6.44, p < 0.00001); that of increased left atrial diameter was 1.25 (95% CI 1.12-1.3, p < 0.0001); that of a long duration of AF before ablation was 1.10 (95% CI 1.04-1.17, p < 0.0009); and that of persistent AF was 2.44 (95% CI 1.30-4.58, p < 0.006). However, there exists significant heterogeneity for each indicator, and a slight publication bias was observed. Conclusions:Our study suggests that early recurrence in the blanking period, increased left atrial size, a long duration of AF before ablation and persistent AF are independent predictors of late recurrence after cryoballoon ablation.

Hematopoietic cell selection based on PIEZO1 expression drives thrombosis risk in type 2 diabetes.

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