Transforming growth factor beta (TGFβ) plays a crucial role in tissue fibrosis. A number of studies have shown that TGFβ3 significantly attenuated tissue fibrosis. However, the mechanism involved in this effect is poorly understood. In this study we found that the expression level of TGFβ3 was higher in human myocardial infarction (MI) tissues than in normal tissues, and interestingly, it increased with the development of fibrosis post‐myocardial infarction (post‐MI). In vitro, human cardiac fibroblasts (CFs) were incubated with angiotensin II (Ang II) to mimic the ischaemic myocardium microenvironment and used to investigate the anti‐fibrotic mechanism of TGFβ3. Then, fibrosis‐related proteins were detected by Western blot. It was revealed that TGFβ3 up‐regulation attenuated the proliferation, migration of human CFs and the expression of collagens, which are the main contributors to fibrosis, promoted the phenotype shift and the cross‐linking of collagens. Importantly, the expression of collagens was higher in the si‐smad7 groups than in the control groups, while silencing smad7 increased the phosphorylation level of the TGFβ/smad signalling pathway. Collectively, these results indicated that TGFβ3 inhibited fibrosis via the TGFβ/smad signalling pathway, possibly attributable to the regulation of smad7, and that TGFβ3 might serve as a potential therapeutic target for myocardial fibrosis post‐MI.

Peroxiredoxin 2 (PRDX2), an inhibitor of reactive oxygen species (ROS), is potentially involved in the progression of atherosclerosis (AS). The aim of this study was to explore the role and mechanism of PRDX2 in AS. The expression of PRDX2 was evaluated in 14 human carotid artery tissues with or without AS. The results showed that the positive reaction of PRDX2 was observed in the carotid artery vascular smooth muscle cells (CAVSMCs). To assess the mechanism by which PRDX2 may function in AS, the CAVSMCs were transfected with pEX4-PRDX2 and si-PRDX2. The catalase, hydrogen peroxide (H₂O₂) scavenger, was used to further confirm that PRDX2-induced inhibitory effects might be mediated through reducing ROS levels. Phenotype alteration and functional testing included transcription testing, immunostaining, and expression studies. The drug of MAPK signaling pathway inhibitors SB203580, SP600125, and PD98059 was used to evaluate the underlying mechanism. In this study, we found that the protein level of PRDX2 and the level of H₂O₂ were higher in the human AS carotid artery tissues than in the normal carotid artery tissues, accompanied with the activation of MAPK signaling pathway. The up-regulation of PRDX2 in the CAVSMCs significantly decreased the expression of ROS, collagen type I (COL I), collagen type III (COL III), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) and inhibited the proliferation, migration, and transformation of the CAVSMCs. The up-regulation of PRDX2 reversed the effect of the CAVSMCs treated with tumor necrosis factor-α (TNF-α). In addition, PRDX2 down-regulation promoted the protein levels of p-p38, p-JNK, and p-ERK, which was confirmed in relevant MAPK inhibitor treatment experiments. Our results suggest a protective role of PRDX2, as a scavenger of ROS, in AS progression through inhibiting the VSMC phenotype alteration and function via MAPK signaling pathway.

Background and Aim: Ischemic heart disease (IHD) remains a critical global public health challenge, yet comparative studies on its burden between younger (20–54 years) and older (55+ years) adults are limited. This study aims to quantify differential IHD burden trajectories across these age groups globally, thereby informing tailored prevention strategies. Methods: Using data from the Global Burden of Disease Study 2021 (GBD), we evaluated the IHD burden through prevalence, disability‐adjusted life years (DALYs), and mortality. Trends from 1990 to 2021 were analyzed via estimated annual percentage change (EAPC), and proportional risk contributions were assessed via population attribution scores. Future trends were projected for the next 30 years via a Bayesian age‐period‐cohort model. Results: From 1990 to 2021, the global DALY rates and mortality rates decreased, whereas the prevalence increased, particularly among younger adults (EAPC = 0.98 [0.93–1.02]). Males presented a greater IHD burden than females did. Low‐ and medium‐socio‐demographic index (SDI) regions experienced greater disease burdens than high‐SDI regions did (EAPC = 1.63 [1.57–1.68]). Metabolic and behavioral risk factors, including high low‐density lipoprotein (LDL) cholesterol (52.74%) and tobacco use (33.90%), are predominant among younger adults, whereas older adults face greater risks from high blood pressure (53.74%) and elevated fasting glucose (16.88%). Projections suggest that mortality will decline in both age groups (20–54 years: 22.92/100,000 population [95% UI: 17.73–28.11]; ≥ 55 years: 404.28/100,000 population [95% UI: 274.18–534.35]), whereas the prevalence will stabilize in older adults but rise and later decline in younger populations. Conclusion: The global IHD burden was associated with decreasing mortality and DALY rates but increasing prevalence, with notable disparities by gender, SDI, and region. Prioritizing age‐specific and targeted interventions is crucial to reversing the prevalence trend and sustaining mortality reductions, ultimately mitigating the global IHD burden.

Excessive inflammation contributes to adverse cardiac remodeling after myocardial infarction (MI), but the mechanisms linking cardiomyocyte injury to immun