N6‑methyladenosine (m6A) is the most prevalent and abundant type of internal post‑transcriptional RNA modification in eukaryotic cells. Multiple types of RNA, including mRNAs, rRNAs, tRNAs, long non‑coding RNAs and microRNAs, are involved in m6A methylation. The biological function of m6A modification is dynamically and reversibly mediated by methyltransferases (writers), demethylases (erasers) and m6A binding proteins (readers). The methyltransferase complex is responsible for the catalyzation of m6A modification and is typically made up of methyltransferase‑like (METTL)3, METTL14 and Wilms tumor 1‑associated protein. Erasers remove methylation by fat mass and obesity‑associated protein and ALKB homolog 5. Readers play a role through the recognition of m6A‑modified targeted RNA. The YT521‑B homology domain family, heterogeneous nuclear ribonucleoprotein and insulin‑like growth factor 2 mRNA‑binding protein serve as m6A readers. The m6A methylation on transcripts plays a pivotal role in the regulation of downstream molecular events and biological functions, such as RNA splicing, transport, stability and translatability at the post‑transcriptional level. The dysregulation of m6A modification is associated with cancer, drug resistance, virus replication and the pluripotency of embryonic stem cells. Recently, a number of studies have identified aberrant m6A methylation in cardiovascular diseases (CVDs), including cardiac hypertrophy, heart failure, arterial aneurysm, vascular calcification and pulmonary hypertension. The aim of the present review article was to summarize the recent research progress on the role of m6A modification in CVD and give a brief perspective on its prospective applications in CVD.

Background: Insulin resistance (IR) is considered a pivotal risk factor for cardiometabolic diseases, and the triglyceride–glucose index (TyG index) has emerged as a reliable surrogate marker of IR. Although several recent studies have shown the association of the TyG index with vascular disease, no studies have further investigated the role of the TyG index in acute ST-elevation myocardial infarction (STEMI). The objective of the present study was to evaluate the potential role of the TyG index as a predictor of prognosis in STEMI patients after percutaneous coronary intervention (PCI). Methods: The study included 1092 STEMI patients who underwent PCI. The patients were divided into 4 quartiles according to TyG index levels. Clinical characteristics, fasting plasma glucose (FPG), triglycerides (TGs), other biochemical parameters, and the incidence of major adverse cardiovascular and cerebral events (MACCEs) during the follow-up period were recorded. The TyG index was calculated using the following formula: ln[fasting TGs (mg/dL) × FPG (mg/dL)/2]. Results: The incidence of MACCEs and all-cause mortality within 30 days, 6 months and 1 year after PCI were higher among STEMI patients with TyG index levels in the highest quartile. The TyG index was significantly associated with an increased risk of MACCEs in STEMI patients within 1 year after PCI, independent of confounding factors, with a value of 1.529 (95% CI 1.001–2.061; P = 0.003) for those in the highest quartile. The area under the curve (AUC) of the TyG index predicting the occurrence of MACCEs in STEMI patients after PCI was 0.685 (95% CI 0.610–0.761; P = 0.001). The results also revealed that Killip class > 1, anaemia, albumin, uric acid, number of stents and left ventricular ejection fraction (LVEF) were independent predictors of MACCEs in STEMI patients after PCI (all P < 0.05). Conclusions: This study indicated an association between higher TyG index levels and increased risk of MACCEs in STEMI patients for the first time, and the TyG index might be a valid predictor of clinical outcomes in STEMI patients undergoing PCI. Trial Registration ChiCTR1900024577.

Ferroptosis is a type of regulated cell death driven by iron dependent accumulation of cellular reactive oxygen species (ROS) when glutathione (GSH)-dependent lipid peroxidation repair systems are compromised. Nuclear receptor co-activator 4 (NCOA4)-mediated selective autophagy of ferritin, termed ferritinophagy, involves the regulation of ferroptosis. Emerging evidence has revealed that ferritinophagy and ferroptosis exert a significant role in the occurrence and development of cardiovascular disease. In the present review, we aimed to present a brief overview of ferritinophagy and ferroptosis focusing on the underlying mechanism and regulations involved. We summarize and discuss relevant research progress on the role of ferritinophagy and ferroptosis in cardiovascular diseases accompanied with potential applications of ferritinophagy and ferroptosis modulators in the treatment of ferroptosis-associated cardiovascular diseases.

Background: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value. Methods: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters. Results: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli’s index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles. Conclusion: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes.

Contrast-induced acute kidney injury (CI-AKI) causes clinically acquired nephropathy in patients who undergo coronary interventions. Hypoxic injury to proximal tubular epithelial cells is a pathological mechanism of CI-AKI. Previous studies have shown that hypoxia activates HIF-1α/HE4/NF-κB to enhance renal fibrosis, and the SGLT-2 inhibitor luseogliflozin inhibits hypoxia-inducible factor (HIF)-1α expression to reduce the progression of diabetic nephropathy. However, the therapeutic effects and mechanisms of SGLT-2 inhibitors on CI-AKI are unclear. We explored the role of the HIF-1α/HE4/NF-κB pathway in CI-AKI and how dapagliflozin effectively treats CI-AKI by inhibiting this pathway. In vitro, cells were divided into the control, hypoxia, hypoxia + dapagliflozin, and hypoxia + pSilencer-HIF-1α groups. Cellular hypoxia, apoptosis, and related protein expression were evaluated by immunofluorescence, western blotting, and flow cytometry, respectively. Dapagliflozin significantly decreased oxygen consumption, HIF-1α, human epididymis protein 4 (HE4), NF-κB expression, and apoptotic cells compared with the control (P < 0.01). In vivo, rats were divided into the control (C), diabetes (D), diabetes + contrast media, and diabetes + contrast media + dapagliflozin groups. Rats in the latter 2 groups were treated with dapagliflozin for 2 days. CI-AKI was induced by intravenously injecting indomethacin, N-nitro-l-arginine methyl ester, and iohexol. The effects of dapagliflozin on CI-AKI rats were elucidated by assessing renal function, H&E staining, and immunohistochemistry. Serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores were increased in diabetes + contrast media rats compared with C, D, and diabetes + dapagliflozin + contrast media rats (P < 0.01). Thus, dapagliflozin may ameliorate CI-AKI through suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo.