ABSTRACT
Background: In the present study, we aimed to find out whether luteolin (Lut) pretreatment could ameliorate myocardial ischemia/reperfusion (I/R) injury by regulating the lncRNA just proximal to XIST (JPX)/microRNA-146b (miR-146b) axis. Methods: We established the models in vitro (HL-1 cells) and in vivo (C57BL/6J mice) to certify the protection mechanism of Lut pretreatment on myocardial I/R injury. Dual luciferase reporter gene assay was utilized for validating that JPX could bind to miR-146b. JPX and miR-146b expression levels were determined by RT-qPCR. Western blot was utilized to examine apoptosis-related protein expression levels, including cleaved caspase-9, caspase-9, cleaved caspase-3, caspase-3, Bcl-2, Bax, and BAG-1. Apoptosis was analyzed by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, as well as flow cytometry. Animal echocardiography was used to measure cardiac function (ejection fraction (EF) and fractional shortening (FS) indicators). Results: miR-146b was demonstrated to bind and recognize the JPX sequence site by dual luciferase reporter gene assay. The expression level of miR-146b was corroborated to be enhanced by H/R using RT-qPCR (P < 0.001 vs. Con). Moreover, JPX could reduce the expression of miR-146b, whereas inhibiting JPX could reverse the alteration (P < 0.001 vs. H/R, respectively). Western blot analysis demonstrated that Lut pretreatment increased BAG-1 expression level and Bcl-2/Bax ratio, but diminished the ratio of cleaved caspase 9/caspase 9 and cleaved caspase 3/caspase 3 (P < 0.001 vs. H/R, respectively). Moreover, the cell apoptosis change trend, measured by Annexin V-APC/7-AAD dualstaining, Hoechst 33342 staining, along with flow cytometry, was consistent with that of apoptosis-related proteins. Furthermore, pretreatment with Lut improved cardiac function (EF and FS) (P < 0.001 vs. I/R, respectively), as indicated in animal echocardiography. Conclusion: Our results demonstrated that in vitro and in vivo, Lut pretreatment inhibited apoptosis via the JPX/miR-146b axis, ultimately improving myocardial I/R injury.
Subject(s)
MicroRNAs , Myocardial Reperfusion Injury , RNA, Long Noncoding , Mice , Animals , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/metabolism , Caspase 3/genetics , Caspase 3/metabolism , Caspase 9/metabolism , Myocytes, Cardiac/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Luteolin/pharmacology , Luteolin/therapeutic use , Luteolin/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , bcl-2-Associated X Protein/metabolism , Annexin A5/metabolism , Mice, Inbred C57BL , Proto-Oncogene Proteins c-bcl-2/metabolism , Luciferases/metabolism , Apoptosis/geneticsABSTRACT
Background: Acute ST-segment elevation myocardial infarction (STEMI) patients after primary PCI were readmitted for revascularization due to non-culprit lesion (NCL) progression. Objective: To develop and validate a nomogram that can accurately predict the likelihood of NCL progression revascularization in STEMI patients following primary PCI. Methods: The study enrolled 1,612 STEMI patients after primary PCI in our hospital from June 2009 to June 2018. Patients were randomly divided into training and validation sets in a 7:3 ratio. The independent risk factors were determined by LASSO regression and multivariable logistic regression analysis. Multivariate logistic regression analysis was utilized to develop a nomogram, which was then evaluated for its performance using the concordance statistics, calibration plots, and decision curve analysis (DCA). Results: The nomogram was composed of five predictors, including age (OR: 1.007 95% CI: 1.005-1.009, P < 0.001), body mass index (OR: 1.476, 95% CI: 1.363-1.600, P < 0.001), triglyceride and glucose index (OR: 1.050, 95% CI: 1.022-1.079, P < 0.001), Killip classification (OR: 1.594, 95% CI: 1.140-2.229, P = 0.006), and serum creatinine (OR: 1.007, 95% CI: 1.005-1.009, P < 0.001). Both the training and validation groups accurately predicted the occurrence of NCL progression revascularization (The area under the receiver operating characteristic curve values, 0.901 and 0.857). The calibration plots indicated an excellent agreement between prediction and observation in both sets. Furthermore, the DCA demonstrated that the model exhibited clinical efficacy. Conclusion: A convenient and accurate nomogram was developed and validated for predicting the occurrence of NCL progression revascularization in STEMI patients after primary PCI.
ABSTRACT
Atherosclerosis is the main cause of cardiovascular diseases that seriously endanger human health. The existing treatment drugs are effective, but they have some side effects. Accumulating evidence suggests that flavonoids have attracted wide attention due to their multiple cardioprotective effects and fewer side effects. PubMed, Web of Science database, Embase, and Cochrane Library were searched for studies evaluating the effects of flavonoids against atherosclerosis. 119 studies published from August 1954 to April 2023 were included. Random-effects models were performed for synthesis. Compared with the control group, flavonoids significantly reduced longitudinal and cross-sectional plaque area. The findings indicated that flavonoids significantly reduced the concentrations of serum TC, TG, and LDL-C and increased serum HDL-C concentrations. Besides, flavonoids reduced the levels of circulating pro-inflammatory factors, including TNF-α, IL-1ß, and IL-6, and increased the serum IL-10 level. This study provides evidence for the potential cardiovascular benefits of flavonoids.
