In recent years, the mechanism of cell death has become a hotspot in research on the pathogenesis and treatment of cardiovascular disease (CVD). Different cell death modes, including autophagy, apoptosis, and pyroptosis, are mosaic with each other and collaboratively regulate the process of CVD. This review summarizes the interaction and crosstalk of key pathways or proteins which play a critical role in the entire process of CVD and explores the specific mechanisms. Furthermore, this paper assesses the interrelationships among these three cell deaths and reviews how they regulate the pathogenesis of CVD. By understanding how these three cell death modes go together we can learn about the pathogenesis of CVD, which will enable us to identify new targets for preventing, controlling, and treating CVD. It will not only reduce mortality but also improve the quality of life.
Background: Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland primarily produces melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptotic, and anti-apoptotic properties. This study examined MT’s anti-oxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine. Methods: In vitro, THP-1 macrophages were induced by 1 µM nicotine to form a pyroptosis model and performed 30 mM MT for treatment. In vivo, ApoE-/- mice were administered 0.1 mg/mL nicotine solution as drinking water, and 1 mg/mL MT solution was intragastric administrated at 10 mg/kg/day. The changes in pyroptosis, apoptosis, and oxidative stress were detected. Results: MT downregulated pyroptosis, whose changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. MT also inhibited apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. Vivo studies confirmed that nicotine could accelerate plaque formation. Moreover, mice treated with MT showed a reduction in AS lesion area. Conclusions: MT alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.
22 July 2022 in Frontiers in Cardiovascular Medicine
Objectives: To undertake a systematic review and meta-analysis of cohort studies to compare the patency and adverse outcomes of sequential and individual saphenous vein grafts (SVGs) in coronary artery bypass grafting (CABG).Methods: We searched PubMed, Embase, and the Cochrane Library for cohort studies. Endpoints for vein graft failure, perioperative and follow-up adverse events were extracted as risk ratio (RR) with 95% confidence intervals (95% CI). Statistical heterogeneity across the studies was examined using the I2 statistic. Potential of publication bias was evaluated quantitatively by the Egger's test. Sensitivity analysis was also performed to assess the robustness of our outcomes.Results: The 15 studies were analyzed, including 22,004 patients, 4,580 grafts, and seven different adverse events under individual or sequential CABG. The sequential group had inferior graft failure (RR = 0.68; 95% CI, 0.60–0.77) and long-term mortality (RR = 0.76; 95%CI, 0.61–0.95), but with an increased risk of perioperative repeat revascularization (RR = 1.58; 95%CI, 1.16–2.14) than the individual group.Conclusion: Taken together, our analysis of the aggregated evidence comparing the sequential and individual saphenous vein grafts for coronary heart disease patients showed that the use of the sequential graft was associated with inferior graft failure and long-term mortality respectively, but with an increased risk of perioperative repeat revascularization. According to our study, both surgical techniques have their own advantages in efficacy and safety, and the selection of surgical techniques should be based on patients and surgeons. Sequential saphenous vein grafts should be more recommended to experienced surgeons in order to both reduce perioperative adverse events and improve long-term patency.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022326992.
Postoperative Atrial Fibrillation (POAF) frequently follows Coronary Artery Bypass Grafting (CABG) surgery. This prospective study investigates genes linked to POAF in CABG patients, aiming to create a predictive model. Employing differential gene and methylation analyses, the study identified four genes (WARS2, CKAP2, CHI3L1, HSD17B6) associated with POAF. Preoperative plasma samples and clinical data were collected from 139 CABG patients, categorized into POAF (+) (43) and POAF (-) (96). Real-time quantitative PCR assessed gene expression, and a predictive model using the LASSO method demonstrated robust performance, with AUC values of 0.8895 in the training set and 0.7840 in the test set. This pioneering study integrates genomics and clinical data, suggesting WARS2, CKAP2, and CHI3L1 as potential indicators for POAF prediction. Graphical