Acute myocardial infarction remains the leading cause of death in humans. Timely restoration of blood perfusion to ischemic myocardium remains the most effective strategy in the treatment of acute myocardial infarction, which can significantly reduce morbidity and mortality. However, after restoration of blood flow and reperfusion, myocardial injury will aggravate and induce apoptosis of cardiomyocytes, a process called myocardial ischemia-reperfusion injury. Studies have shown that the loss and death of cardiomyocytes caused by oxidative stress, iron load, increased lipid peroxidation, inflammation and mitochondrial dysfunction, etc., are involved in myocardial ischemia-reperfusion injury. In recent years, with the in-depth research on the pathology of myocardial ischemia-reperfusion injury, people have gradually realized that there is a new form of cell death in the pathological process of myocardial ischemia-reperfusion injury, namely ferroptosis. A number of studies have found that in the myocardial tissue of patients with acute myocardial infarction, there are pathological changes closely related to ferroptosis, such as iron metabolism disorder, lipid peroxidation, and increased reactive oxygen species free radicals. Natural plant products such as resveratrol, baicalin, cyanidin-3-O-glucoside, naringenin, and astragaloside IV can also exert therapeutic effects by correcting the imbalance of these ferroptosis-related factors and expression levels. Combining with our previous studies, this review summarizes the regulatory mechanism of natural plant products intervening ferroptosis in myocardial ischemia-reperfusion injury in recent years, in order to provide reference information for the development of targeted ferroptosis inhibitor drugs for the treatment of cardiovascular diseases.

Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (H₂S) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which H₂S improves the progression of atrial fibrosis to AF remains unclear. A case-control study of patients with and without AF was designed to assess changes in H₂S, the Warburg effect, and ERS in AF. The results showed that AF can significantly reduce cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate thiotransferase (3-MST) expression and the H₂S level, induce cystathionine-β-synthase (CBS) expression; increase the Warburg effect, ERS and atrial fibrosis; and promote left atrial dysfunction. In addition, AngII-treated SD rats had an increased Warburg effect and ERS levels and enhanced atrial fibrosis progression to AF compared to wild-type SD rats, and these conditions were reversed by sodium hydrosulfide (NaHS), dichloroacetic acid (DCA) or 4-phenylbutyric acid (4-PBA) supplementation. Finally, low CSE levels in AngII-induced HL-1 cells were concentration- and time-dependent and associated with mitochondrial dysfunction, apoptosis, the Warburg effect and ERS, and these effects were reversed by NaHS, DCA or 4-PBA supplementation. Our research indicates that H₂S can regulate the AngII-induced Warburg effect and ERS and might be a potential therapeutic drug to inhibit atrial fibrosis progression to AF.

N⁶-methyladenosine (m⁶A) methylation is one of the most predominant internal RNA modifications in eukaryotes and has become a hot spot in the field of epigenetics in recent years. Cardiovascular diseases (CVDs) are a leading cause of death globally. Emerging evidence demonstrates that RNA modifications, such as the m⁶A modification, are associated with the development and progression of many diseases, including CVDs. An increasing body of studies has indicated that programmed cell death (PCD) plays a vital role in CVDs. However, the molecular mechanisms underlying m⁶A modification and PCD in CVDs remain poorly understood. Herein, elaborating on the highly complex connections between the m⁶A mechanisms and different PCD signaling pathways and clarifying the exact molecular mechanism of m⁶A modification mediating PCD have significant meaning in developing new strategies for the prevention and therapy of CVDs. There is great potential for clinical application.

Perivascular adipose tissue (PVAT) is increasingly recognized as an active vascular regulator that influences inflammation, metabolism, and atherosclerotic progression. In healthy vessels, PVAT displays brown adipose-like features and contributes to vascular protection, whereas PVAT dysfunction is associated with adipose whitening, inflammatory activation, and enhanced plaque formation. Circadian clock genes are major regulators of tissue metabolism, yet their role in PVAT biology and atherosclerosis remains incompletely understood. Here, we investigated the function of the core circadian factor BMAL1 in brown adipocytes and PVAT using a brown adipocyte-specific BMAL1 knockout model (Bmal1^BAKO) and ApoE-deficient atherosclerosis-prone mice. Transcriptomic profiling of thoracic aortic PVAT and abdominal aortic PVAT revealed that BMAL1 deficiency induces a shift in metabolic gene expression profiles characterized by upregulation of glycolytic and lipogenic gene programs, together with suppression of genes linked to thermogenic and vascular homeostasis. Mechanistically, BMAL1 loss increased Mlxipl (encoding ChREBP) expression, and ChREBP knockdown attenuated the glycolytic–lipogenic transcriptional response to BMAL1 depletion in cultured brown adipocytes. In parallel, BMAL1-deficient PVAT exhibited enlarged lipid droplets, increased oxidative stress-related transcriptional profile, and inflammatory remodeling accompanied by macrophage accumulation. In ApoE^−/− mice, brown adipocyte-specific BMAL1 deletion aggravated atherosclerotic lesion formation in both chow-fed aging mice and Western diet-fed young mice, without major changes in systemic energy balance. In conclusion, brown adipocyte BMAL1 deficiency was associated with ChREBP-linked metabolic reprogramming, loss of brown-like PVAT features, oxidative and macrophage-associated remodeling, and increased atherosclerosis.