Myocardial infarction (MI) is one of the leading causes of death. Wilms' tumor 1-associating protein (WTAP), one of the components of the m 6 A methyltransferase complex, has been shown to affect gene expression via regulating mRNA modification. Although WTAP has been implicated in various diseases, its role in MI is unclear. In this study, we found that hypoxia/reoxygenation (H/R) time-dependently increased WTAP expression, which in turn promoted endoplasmic reticulum (ER) stress and apoptosis, in human cardiomyocytes (AC16). H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA. We then investigated the underlying molecular mechanism and found that WTAP affected m 6 A methylation of ATF4 mRNA to regulate its expression, and that the inhibitory effects of WTAP on ER stress and apoptosis were ATF4 dependent. Finally, WTAP’s effects on myocardial I/R injury were confirmed in vivo . WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m 6 A modification of ATF4 mRNA. These findings highlight the importance of WTAP in I/R injury and provide new insights into therapeutic strategies for MI.

No abstract

Background The association between the quantitative flow ratio (QFR) and adverse events after drug‐coated balloon (DCB) angioplasty for in‐stent restenosis (ISR) lesions has not been investigated. Hypothesis Post‐procedural QFR is related to adverse events in patients undergoing DCB angioplasty for ISR lesions. Methods This retrospective study included data from patients undergoing DCB angioplasty for drug‐eluting stent (DES) ISR between January 2016 and February 2019. The QFR was measured at baseline and after DCB angioplasty. The endpoint was the vessel‐oriented composite endpoint (VOCE), defined as a composite of cardiac death, vessel‐related myocardial infarction, and ischemia‐driven target vessel revascularization. Results Overall, 177 patients with 185 DES‐ISR lesions were included. During 1‐year follow‐up, 27 VOCEs occurred in 26 patients. The area under curve (AUC) of the post‐procedural QFR was statistically greater than that of the in‐stent percent diameter stenosis (0.77, 95% confidence interval [CI] 0.67–0.87 vs. 0.64, 95% CI 0.53–0.75; p = .032). Final QFR cutoff of 0.94 has the best predictive accuracy for VOCE. A QFR > 0.94 was associated with a lower risk of VOCE compared to a QFR ≤ 0.94 (log‐rank test, p < .0001). Survival analysis using the multivariable Cox model showed that a post‐procedural QFR ≤ 0.94 was an independent predictor of 1‐year VOCE (hazard ratio 6.53, 95% CI 2.70–15.8, p < .001). Conclusions A lower QFR value was associated with worse clinical outcomes at 1 year after DCB angioplasty for DES‐ISR.