Biointerface topography regulates phenotypic switching and cell apoptosis in vascular smooth muscle cells

Background: In-stent restenosis (ISR) is a complex disease that occurs after coronary stenting procedures. The development of quality materials and improvement of our understanding on significant factors regulating ISR are essential for enhancing prognosis. Vascular smooth muscle cells (VSMCs) are the main constituent cells of blood vessel walls, and dysfunction of VMSCs can exacerbate ISR. Accordingly, in this study, we explored the influence of wrinkled material topography on the biological functions of VSMCs. Methods: Polydimethylsiloxane with a wrinkled topography was synthesized using elastomer base and crosslinking and observed by atomic force microscopy. VSMC proliferation, apoptosis, and morphology were determined by Cell Counting Kit-8 assays, fluorescence-assisted cell sorting, and phalloidin staining. α-Smooth muscle actin (α-SMA), major histocompatibility complex (MHC), and calponin 1 (CNN-1) expression levels were measured by quantitative real-time polymerase chain reaction and western blotting. Moreover, p53 and cleaved caspase-3 expression levels were evaluated by western blotting in VSMCs to assess apoptotic induction. Results: Surface topographies were not associated with a clear orientation or elongation of VSMCs. The number of cells was increased on wrinkled surfaces (0.7 μm in amplitude, and 3 μm in wavelength [W3]) compared with that on other surfaces, contributing to continuously increased cell proliferation. Moreover, interactions of VSMCs with the W3 surface suppressed phenotypic switching, resulting in ISR via regulation of α-SMA, calponin-1, and SM-MHC expression. The surface with an amplitude of 0.05 μm and a wavelength of 0.5 μm (W0.5) promoted apoptosis by inducing caspase 3 and p53 activities. Conclusion: Introduction of aligned topographies on biomaterial scaffolds could provide physical cues to modulate VSMC responses for engineering vascular constructs. Materials with wrinkled topographies could have applications in the development of stents to reduce ISR

Association of age at menarche with valvular heart disease: An analysis based on electronic health record (CREAT2109)

BackgroundThe association between age at menarche and coronary heart disease has been reported, but the association between age at menarche and valvular heart disease (VHD) has not been described. We aimed to examine the association between age at menarche and VHD.MethodsBy collecting data from four medical centers of the Affiliated Hospital of Qingdao University (QUAH) from January 1, 2016, to December 31, 2020, we sampled 105,707 inpatients. The main outcome of this study was newly diagnosed VHD, which was diagnosed based on ICD-10 coding, and the exposure factor was age at menarche, which was accessed through the electronic health records. We used logistic regression model to investigate the association between age at menarche and VHD.ResultsIn this sample (mean age 55.31 ± 13.63 years), the mean age at menarche was 15. Compared with women with age at menarche 14–15 years, the odds ratio of VHD in women with age at menarche ≤13, 16–17, and ≥18 years was 0.68 (95% CI 0.57–0.81), 1.22 (95% CI 1.08–1.38), and 1.31 (95% CI 1.13–1.52), respectively (P for all < 0.001). By restricting cubic splines, we found that later menarche was associated with increased odds of VHD (P < 0.001). Furthermore, in subgroup analysis of different etiologies, the similar trend persisted for non-rheumatic VHD.ConclusionsIn this large inpatient sample, later menarche was associated with higher risk of VHD

Transcatheter versus surgical aortic valve replacement in patients with aortic regurgitation: A propensity-matched analysis

This study aimed to analyze in-hospital and early-to-interim outcomes of pure aortic regurgitation (AR) using transcatheter aortic valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR). Background: Few studies have discussed and compared the safety and short-term prognosis of TAVR and SAVR in pure AR patients. As such, we looked to the National Readmissions Database (NRD) for records between 2016 and 2019 in order to identify patients diagnosed with pure AR who underwent SAVR or TAVR. We used the propensity score matching to minimize disparities between two groups. We included 23,276 pure AR patients: 1983 (8.5%) who underwent TAVR and 21,293 (91.5%) who underwent SAVR. We found 1820 matched pairs using propensity score matching. In the matching cohort, TAVR was associated with a low risk of in-hospital mortality. Although TAVR had lower incidences of 30-day all-cause readmission (hazard ratio (HR):0.73, 95% confidence interval (CI): 0.61–0.87; P < 0.01) and 6-month all-cause readmission (HR: 0.81, 95% CI: 0.67–0.97; P = 0.03), while TAVR had high incidences of 30-day permanent pacemaker implantation incidence (HR: 3.54, 95% CI: 1.62–7.74; P < 0.01) and 6-month permanent pacemaker implantation incidence (HR: 4.12, 95% CI: 1.17–14.4; P = 0.03).In conclusion, TAVR and SAVR had similar risks of hospital death and lower rates of 30-day and 6-month all-cause and cardiovascular readmission. But TAVR had a higher risk of permanent pacemaker implantation than SAVR in AR patients, suggesting that TAVR can be performed safely in pure AR patients

Protective effect of ischaemic postconditioning combined with nicorandil on myocardial ischaemia‒reperfusion injury in diabetic rats

Abstract Background The diabetic heart exhibits a high sensitivity to ischaemia/reperfusion (I/R) injury. Diabetes mellitus (DM) can affect the efficacy of cardioprotective interventions and reduce the therapeutic potential of existing treatment options. This study aimed to investigate the feasibility of shifting from monotherapy to combination therapy in diabetic myocardial I/R injury. Methods 6–8 week rats were randomized into 10 groups: sham, I/R, ischaemia postconditioning (I-Post), nicorandil (Nic), combination therapy (I-Post + Nic), DM sham, DM I/R, DM I-Post, DM Nic and DM I-Post + Nic. The extent of myocardial injury was clarified by measuring CK-MB and NO levels in plasma, ROS content in myocardial tissues, and TTC/Evans Blue staining to assess the area of myocardial infarction. Pathological staining of cardiac tissue sections were performed to clarify the structural changes in myocardial histopathology. Finally, Western blotting was performed to detect the phosphorylation levels of some key proteins in the PI3K/Akt signalling pathway in myocardial tissues. Results We confirms that myocardial injury in diabetic I/R rats remained at a high level after treatment with I-Post or nicorandil alone. I-Post combined with nicorandil showed better therapeutic effects in diabetic I/R rats, and the combined treatment further reduced the area of myocardial injury in diabetic I/R rats compared with I-Post or nicorandil treatment alone (P < 0.001), as well as the levels of the myocardial injury markers CK-MB and ROS (P < 0.001); it also significantly increased plasma NO levels. Pathological staining also showed that diabetic rats benefited significantly from the combination therapy. Further mechanistic studies confirmed this finding. The protein phosphorylation levels of PI3K/Akt signalling pathway in the heart tissue of diabetic I/R rats were significantly higher after the combination treatment than after one treatment alone (all P < 0.05). Conclusion I-Post combined with nicorandil treatment maintains effective cardioprotection against diabetic myocardial I/R injury by activating the PI3K/Akt signalling pathway

The TFPI2–PPARγ axis induces M2 polarization and inhibits fibroblast activation to promote recovery from post-myocardial infarction in diabetic mice

Abstract Background Diabetes mellitus is one of the causes of poor ventricular remodelling and poor cardiac recovery after myocardial infarction (MI). We previously reported that tissue factor pathway inhibitor-2 (TFPI2) was downregulated in response to hyperglycaemia and that it played a pivotal role in extracellular matrix (ECM) degradation and cell migration. Nonetheless, the function and mechanism of TFPI2 in post-MI remodelling under diabetic conditions remain unclear. Therefore, in the present study, we investigated the role of TFPI2 in post-MI effects in a diabetic mouse model. Results TFPI2 expression was markedly decreased in the infarcted myocardium of diabetic MI mice compared with that in non-diabetic mice. TFPI2 knockdown in the MI mouse model promoted fibroblast activation and migration as well as matrix metalloproteinase (MMP) expression, leading to disproportionate fibrosis remodelling and poor cardiac recovery. TFPI2 silencing promoted pro-inflammatory M1 macrophage polarization, which is consistent with the results of TFPI2 downregulation and M1 polarization under diabetic conditions. In contrast, TFPI2 overexpression in diabetic MI mice protected against adverse cardiac remodelling and functional deterioration. TFPI2 overexpression also inhibited MMP2 and MMP9 expression and attenuated fibroblast activation and migration, as well as excessive collagen production, in the infarcted myocardium of diabetic mice. TFPI2 promoted an earlier phenotype transition of pro-inflammatory M1 macrophages to reparative M2 macrophages via activation of peroxisome proliferator-activated receptor gamma. Conclusions This study highlights TFPI2 as a promising therapeutic target for early resolution of post-MI inflammation and disproportionate ECM remodelling under diabetic conditions

Datasheet1_Association of age at menarche with valvular heart disease: An analysis based on electronic health record (CREAT2109).docx

BackgroundThe association between age at menarche and coronary heart disease has been reported, but the association between age at menarche and valvular heart disease (VHD) has not been described. We aimed to examine the association between age at menarche and VHD.MethodsBy collecting data from four medical centers of the Affiliated Hospital of Qingdao University (QUAH) from January 1, 2016, to December 31, 2020, we sampled 105,707 inpatients. The main outcome of this study was newly diagnosed VHD, which was diagnosed based on ICD-10 coding, and the exposure factor was age at menarche, which was accessed through the electronic health records. We used logistic regression model to investigate the association between age at menarche and VHD.ResultsIn this sample (mean age 55.31 ± 13.63 years), the mean age at menarche was 15. Compared with women with age at menarche 14–15 years, the odds ratio of VHD in women with age at menarche ≤13, 16–17, and ≥18 years was 0.68 (95% CI 0.57–0.81), 1.22 (95% CI 1.08–1.38), and 1.31 (95% CI 1.13–1.52), respectively (P for all ConclusionsIn this large inpatient sample, later menarche was associated with higher risk of VHD.</p