Phenotypic switch of vascular smooth muscle cells (VSMCs) plays an important role in the pathogenesis of atherosclerosis and aortic dissection. However, the mechanisms of phenotypic modulation are still unclear. MicroRNAs have emerged as important regulators of VSMC function. We recently found that microRNA-124 (miR-124) was downregulated in proliferative vascular diseases that were characterized by a VSMC phenotypic switch. Therefore, we speculated that the aberrant expression of miR-124 might play a critical role in human aortic VSMC phenotypic switch. Using quantitative RT-PCR, we found that miR-124 was dramatically downregulated in the aortic media of clinical specimens of the dissected aorta and correlated with molecular markers of the contractile VSMC phenotype. Overexpression of miR-124 by mimicking transfection significantly attenuated platelet-derived growth factor-BB-induced human aortic VSMC proliferation and phenotypic switch. Furthermore, we identified specificity protein 1 (Sp1) as the downstream target of miR-124. A luciferase reporter assay was used to confirm direct miR-124 targeting of the 3′-untranslated region of the Sp1 gene and repression of Sp1 expression in human aortic VSMCs. Furthermore, constitutively active Sp1 in miR-124-overexpressing VSMCs reversed the antiproliferative effects of miR-124. These results demonstrated a novel mechanism of miR-124 modulation of VSMC phenotypic switch by targeting Sp1 expression. NEW & NOTEWORTHY Previous studies have demonstrated that miR-124 is involved in the proliferation of a variety of cell types. However, miRNAs are expressed in a tissue-specific manner. We first identified miR-124 as a critical regulator in human aortic vascular smooth muscle cell differentiation, proliferation, and phenotype switch by targeting the 3′-untranslated region of specificity protein 1.

Background: Dual antiplatelet therapy (DAPT) improves early post-operative graft patency, but the optimal DAPT strategy for the patients after coronary artery bypass grafting (CABG) has not been confirmed. We sought to evaluate the effect of aspirin plus ticagrelor versus aspirin plus clopidogrel on saphenous vein graft (SVG) patency within 1 year after CABG. Methods: Between October 2017 and December 2018, 147 consecutive patients undergoing elective CABG at Changhai Hospital were randomized into two groups: group AT, receiving aspirin 100 mg/d plus ticagrelor 2×90 mg/d; group AC, receiving aspirin 100 mg/d plus clopidogrel 75 mg/d. Both DAPTs should be administered within 24 h when clinical stability was ensured. 64-multislice computed tomography angiography (MSCTA) was used to assess the graft patency at 12 months after CABG.CYP2C19 gene variants were measured to assess the clopidogrel efficacy on graft patency. Results: Among the 147 participants who completed the study, one (0.7%) patient from the AC group died at 5 weeks after surgery due to severe infection. All other patients were treated with DAPT for 12 months and underwent 64-MSCTA according to schedule. There were no significant differences in pre-operative characteristics and intraoperative transit-time flow measurement findings between the two groups. Besides, no significant differences in the incidence of major adverse cardiac events (MACEs) and major bleeding were observed. A 64-MSCTA showed that SVG patency was 91.0% (141 of 155) in the AT group and 89.9% (161 of 179) in the AC group (P=0.751). No significant associations were found between different CYP2C19 genotypes and SVG patency (P>0.05). Conclusions: Either aspirin plus ticagrelor or aspirin plus clopidogrel can maintain a fairly high graft patency rate in the early phase after CABG, regardless of CYP2C19 genotypes.

To compare mitral valve (MV) repair and concomitant maze procedure with catheter ablation in treating patients with atrial functional mitral regurgitation (AFMR). We retrospectively identified 126 patients with AFMR from January 2012 to December 2015. Of these patients, 60 patients underwent MV repair and concomitant maze procedure, and 66 patients received catheter ablation. Patients were followed up for 7.98 ± 2.01 years. The survival, readmission of heart failure (HF), persistent atrial fibrillation (AF), persistent moderate-severe mitral regurgitation (MR) and tricuspid Regurgitation (TR), and echocardiographic data were analyzed in the follow-up. Predictors of readmission of HF were analyzed. There was no significant difference in baseline and echocardiographic characteristics, in-hospital mortality, and other adverse events postoperatively between two groups. The surgical group was associated with lower rates of MR > 2 + grade either at discharge (P = 0.0023) or in the follow-up (P = 0.0001). There was no significant difference in the incidence of overall survival between the two groups. The surgical group was associated with a lower rate of readmission of HF and AF in the follow-up. Univariable and multivariable analysis confirmed AF at discharge, moderate-severe MR at discharge, no MV surgery, moderate-severe TR at discharge, and LA volume as predictors of readmission of HF. Both groups experienced significant reverse cardiac remodeling. Our results suggest that for the treatment of AFMR with persistent or long-standing persistent AF and moderate-severe MR, MV repair and concomitant maze procedure may achieve a better outcome than catheter ablation procedure.

Acute aortic dissection (AAD) represents a cardiovascular ailment characterised by a notable mortality rate. Chronobiological patterns can offer a predictive framework for anticipating the onset of AAD. Data were gathered from 1,151 patients diagnosed with AAD at Changhai Hospital in Shanghai, China, spanning 2000-2023. The χ² test was used to assess whether specific periods exhibited significantly different seasonal/weekly distributions compared with others. Fourier models were utilised for the analysis of rhythmicity in monthly/circadian distribution. Publicly available genome-wide association studies datasets were used to establish the causal relationship between chronotype and AAD. Two sets of genetics instruments were used for analysis, derived from publicly available genetic summary data: 75 single-nucleotide polymorphisms (SNPs) significantly associated with chronotype; and SNPs associated with AAD in the FinnGen consortium. The mean age was 51.5±13.8 years, with 665 patients (57.8%) aged <55 years. Among the 1,151 patients, 80.9% were male. The distribution of DeBakey types was 73.2% (843) for DeBakey I, 21% (242) for DeBakey II, and 5.7% (66) for DeBakey III. Comorbidities included hypertension in 58.5% (673 cases) and diabetes in 7.8% (90 cases). A peak occurred during colder periods (winter/December), and a trough was noted in warmer periods (summer/June). Weekly distribution exhibited no significant variation. Fourier analysis revealed a statistically significant circadian variation (p<0.0001) with a trough between 23:00 and 00:00, a prominent peak from 07:00 to 08:00, and a minor peak between 20:00 and 21:00. Subgroup analyses identified circadian rhythmicity in all subgroups, except for the DeBakey III group and the female group. Using the 75 chronotype-related SNPs, evidence was found of a potential causal effect of chronotype on the risk of AAD, as the inverse-variance weighting analysis showed that self-report chronotype of morningness was associated with a decreased risk of AAD. The findings substantiate that the initiation of AAD displays noteworthy seasonal, monthly, and circadian patterns. The Mendelian randomisation analysis also indicated that the onset of acute aortic dissection is related to circadian rhythm. These findings offer a fresh perspective, facilitating the identification of triggering factors for AAD and bolstering preventive measures for this catastrophic event.