Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and dyslipidemia is one of the major risk factors

Objective: Baoyuan decoction (BYD) is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests. The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction (MI). Methods: Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation. Oxygen-glucose deprivation/recovery (OGD/R) model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD. Results: BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI. Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway. Conclusions: Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways. They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.

Polyunsaturated fatty acid‐derived oxylipins regulate systemic inflammation and exert cardiovascular effects, yet their role in ST‐segment elevation myocardial infarction (STEMI) remains unclear. Herein, we used targeted metabolomics and machine learning algorithms to develop an oxylipin‐based risk model to accurately predict recurrent major adverse cardiovascular events (MACE) after STEMI in two independent prospective cohorts with 2 years of follow‐up. The in vivo effects of significant oxylipin predictors were explored via a murine myocardial ischemia‒reperfusion model and functional metabolomics. Among the 130 plasma oxylipins detected in discovery cohort (n = 645), patients with and without recurrent MACE exhibited significant differences in a variety of oxylipin subclasses. We constructed an oxylipin‐based prediction model that showed powerful performance in predicting recurrent MACE in the discovery cohort (predictive accuracy: 91.5%). The predictive value of the oxylipin marker panel was confirmed in an independent external validation cohort (predictive accuracy: 89.9%; n = 401). Furthermore, we found that the anti‐inflammatory/pro‐resolving oxylipin (ARO) predictor panel showed better prognostic performance than the pro‐inflammatory oxylipin predictor panel in both cohorts. Compared with the treatment of pro‐inflammatory oxylipin predictor panel, combined treatment of six ARO predictors, including 14,15 epoxy‐eicosatrienoic acid, 14(15)‐epoxy‐eicosatetraenoic acid, 12,13‐epoxy‐octadecenoic acid, lipoxin A4, resolving D1, and 6 keto‐prostaglandin F1 showed significant cardiac activities and synergistic metabolic actions in myocardial infarction‒reperfusion model mice. We also mechanistically identified an important role of ARO predictors in restraining ceramide/lysophosphatidylcholine synthesis and inhibiting inflammatory responses. Overall, the present study depicted the landscape of oxylipin profiles in the largest panel of STEMI patients worldwide. Our results also highlight the great potential of bioactive oxylipins in prognostic prediction and therapeutics after STEMI.

Dynamic Modeling of Biotechnical Process Based on Online Support Vector Machine