Paeoniflorin suppresses the apoptosis and inflammation of human coronary artery endothelial cells induced by oxidized low-density lipoprotein by regulating the Wnt/ß-catenin pathway.

CONTEXT: Paeoniflorin (PF) contributes to improving coronary artery disease (CAD). OBJECTIVE: This study clarified the efficiency of PF in CAD and the molecular mechanism. MATERIALS AND METHODS: Human coronary artery endothelial cells (HCAECs) were treated with oxidized low-density lipoprotein (ox-LDL; 20, 40, 80 and 160 µg/mL) and PF (0.05, 0.1 0.2 and 0.4 mM). To study cell phenotypes, HCAECs were treated with 80 µg/mL ox-LDL with or without 0.1 mM PF for 24 h, and cell viability and apoptosis were evaluated using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. In addition, inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). Western blot evaluated the Wnt/ß-catenin pathway-related factors. RESULTS: ox-LDL and PF (0.2 and 0.4 mM) suppressed cell viability in a dose-dependent manner. The IC50 value of PF was 722.9 nM. PF facilitated cell viability (115.76%), inhibited apoptosis (46.28%), reduced IL-6 (63.43%) and IL-8 (66.70%) levels and increased IL-10 levels (181.15%) of ox-LDL-treated HCAECs. Additionally, PF inactivated the Wnt/ß-catenin pathway, and XAV939 treatment further promoted cell viability (120.54%), suppressed apoptosis (56.92%), reduced the levels of IL-6 (76.16%) and IL-8 (86.82%) and increased the IL-10 levels (120.22%) of ox-LDL-induced HCAECs after PF treatment. Moreover, PF alleviated plaque lesions of the aorta and aorta root and serum lipid of ApoE-/- mice with a high-fat diet. DISCUSSION AND CONCLUSIONS: This study first revealed that PF inhibited ox-LDL-induced HCAECs apoptosis and inflammation via the Wnt/ß-catenin pathway and alleviated CAD, suggesting the potential of PF as a drug for CAD treatment.

Different Lipid Parameters in Predicting Clinical Outcomes in Chinese Statin-Naïve Patients After Coronary Stent Implantation.

Background: Low-density lipoprotein cholesterol (LDL-C) is a critical surrogate outcome for cardiovascular disease (CVD). Recent observational studies identified different predictive lipid parameters, but these have not been fully validated in the Chinese population. This study aimed to compare the predictive value of lipid parameters for cardiovascular outcomes in Chinese statin-naïve patients who underwent percutaneous coronary intervention (PCI). Methods: We retrospectively recruited statin-naïve patients who underwent PCI for stable angina and acute coronary syndrome at Sichuan Provincial People's Hospital between 1 January 2016 and 31 December 2017. A follow-up was conducted via outpatient visits or telephone. We divided patients into three groups based on lipid parameter tertiles. We calculated the hazard ratios (HRs) of the highest and lowest tertiles for major adverse cardiovascular events (MACEs) using multivariate Cox proportional hazards regression. We compared the association strength of lipid parameters with MACEs using the HR of non-LDL-C lipid parameters relative to LDL-C. Results: Among 445 included patients, the highest LDL-C, LDL-C/high-density lipoprotein cholesterol (HDL-C), atherosclerosis index, and non-HDL-C level tertiles were associated with an average increase of 165% (HR 2.65, confidence interval [CI] 1.26 to 5.61; P = 0.01), 324% (HR 4.24, CI 1.89 to 9.52; P < 0.001), 152% (HR 2.52, CI 1.22 to 5.22; P = 0.01), and 125% (HR 2.25, CI 1.09 to 4.64; P = 0.01) in the hazard of composite CVD, respectively. Lipoprotein (a) levels did not show a significant association with the endpoints. Except for LDL-C/HDL-C, different lipid parameter HR ratios were <1.0; none were statistically significant. Conclusion: Compared with non-LDL-C lipid parameters, LDL-C acts better predictive value for cardiovascular outcomes in general Chinese statin-naïve post-PCI patients.