Macrophage activation plays a central role in neoatherosclerosis and in‐stent restenosis after percutaneous coronary intervention (PCI). Galectin‐3, mainly expressed on macrophages, is an important regulator of inflammation. This study aimed to investigate the effects of berberine (BBR) on oxidized low‐density lipoprotein (ox‐LDL)‐induced macrophage activation and galectin‐3 expression and their underlying mechanisms. THP‐1‐derived macrophages were pretreated with BBR prior to stimulation with ox‐LDL. Galectin‐3 expression was measured by real‐time PCR, Western blotting, and confocal microscopy. Macrophage activation was assessed by lipid accumulation, expression of inflammatory cytokines, and CD11b and CD86. Plasma galectin‐3 levels were measured in patients undergoing PCI at baseline and after BBR treatment for 3 months. BBR suppressed ox‐LDL‐induced upregulation of galectin‐3 and macrophage activation. Overexpression of galectin‐3 intervened the inhibitory effect of BBR on macrophage activation. BBR activated phospho‐AMPK and inhibited phospho‐NF‐κB p65 nuclear translocation. AMPK inhibition and NF‐κB activation abolished the inhibitory effects of BBR on galectin‐3 expression and macrophage activation. Combination of BBR and rosuvastatin exerted greater effects than BBR or rosuvastatin alone. However, BBR treatment did not further reduce plasma galectin‐3 after PCI in patients receiving standard therapy. In conclusion, BBR alleviates ox‐LDL‐induced macrophage activation by downregulating galectin‐3 via the NF‐κB and AMPK signaling pathways.

Aims  Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose–response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients. Methods and results  Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose–response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21–1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels. Conclusions  In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted. Trial registration ClinicalTrials.gov Identifier: NCT02306616

We evaluated the association of preprocedure CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, and sex) score with ischemic events in patients undergoing percutaneous coronary intervention (PCI). The Dryad Digital Repository enrolled 2533 patients between July 2009 and August 2011. We recorded 1-year ischemic events. Univariate and multivariable logistic regression analyses were used to analyze the association between CHA2DS2-VASc score and ischemic events. Receiver operating characteristic curves were used to evaluate the accuracy of CHA2DS2-VASc score in predicting long-term ischemic events. Long-term death (9.5 vs 2.8%), cardiac death (2.9 vs 1.4%), and nonfatal stroke (1.9 vs 0.7%) were significantly higher in the CHA2DS2-VASc score ≥2 group than the CHA2DS2-VASc score ≤1 group. The CHA2DS2-VASc score was a predictor for all-cause death (odds ratio [95% confidence interval]: 3.71 [1.89-7.30]). The risk factors for all-cause death in CHA2DS2-VASc score ≥2 patients included age, diagnosis, heart failure, older myocardial infarction, diabetes, and chronic obstructive pulmonary disease, while the risk factor for CHA2DS2-VASc score ≤1 patients was age. In conclusion, the CHA2DS2-VASc score is associated with long-term all-cause death, cardiac death, and stroke in patients undergoing PCI, and it may have a potential use for risk stratification for patients who undergo PCI.

Endothelial progenitor cells (EPCs) have the potential to repair damaged blood vessels and promote angiogenesis. Smoking, an important risk factor for cardiovascular diseases, is associated with impaired functions of EPCs. However, the underlying mechanisms remain unclear. The aim of the study was to investigate the effects of cigarette smoke extract (CSE) on autophagy and dysfunction of EPCs and the involvement of galectin-3 in its effects. EPCs were treated with 8% CSE for 24 h (without affecting cell viability). EPC functions were assessed by tube formation and migration capacity and intracellular ROS and eNOS expression. Autophagy was assessed by autophagic protein expression by Western blotting and immunofluorescence microscopy and autophagosome accumulation by transmission electron microscopy. Galectin-3 expression was measured by real-time PCR, Western blotting, and immunofluorescence microscopy, while phospho-AMPK and phospho-mTOR were measured by Western blotting. EPCs were transfected by shRNA-Gal-3 or shRNA-NC before treatment with CSE to examine the effects of galectin-3 on CSE-induced autophagy and dysfunction of EPCs. CSE-treated EPCs showed decreased tube formation and migration ability and eNOS expression but increased oxidative stress. CSE also induced autophagy which was characterized by a decrease in p62 protein, an increase in LC3B-II/I ratio, and accumulation of autophagosomes. CSE upregulated galectin-3 expression on EPCs. Inhibition of galectin-3 abrogated CSE-induced autophagy and dysfunction of EPCs. CSE activated phospho-AMPK and inhibited phospho-mTOR, and inhibition of galectin-3 abolished CSE's effect on activating phospho-AMPK and inhibiting phospho-mTOR. In conclusion, our results suggest that galectin-3 mediates CSE-induced EPC autophagy and dysfunction, likely via the AMPK/mTOR signaling pathway.

We investigated the independent and combined association of resting heart rate (RHR expressed as beats/min, bpm) and body mass index (BMI) with SYNTAX score (SS) in patients with stable angina. We divided 312 patients into 4 groups according to RHR quartiles: Q1 (<65 bpm), Q2 (65-69 bpm), Q3 (70-79 bpm), and Q4 (≥80 bpm). The SS (12.0 ± 9.0, 16.0 ± 15.5, 18.0 ± 16.5, and 20.0 ± 27.5; P < .001) was significantly higher for those in Q4 than for those in Q1, Q2, and Q3. Multivariate logistic regression analysis indicated that each 10-bpm increment in RHR was significantly associated with SS (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.27-2.06). Patients with high RHR and high BMI had significantly greater odds ratio (OR) of high SS (4.03, 95% CI 2.00-8.14), compared to participants with low RHR and low BMI. Both RHR and BMI were independent predictors of coronary atherosclerosis as assessed by SS. RHR in combination with BMI and multivariate logistic regression analysis emphasized the importance of the correlation between RHR and SS in patients with stable angina pectoris.