Galectin-3 plays an important role in atherosclerosis. Upregulation of VSMCs calcification is involved in the progression and development of vulnerable plaques. Thioredoxin-interacting protein (TXNIP) has been regarded as an important determinant in regulating inflammation and oxidative stress. In this study, we evaluated the role of TXNIP in galectin-3-induced vascular calcification. A primary culture of mouse VSMCs was established by enzymatic digestion of aorta. Small interfering (si) RNA was used to knock down the expression of target gene. VSMCs were treated with 3-methyladenine (3-MA) or compound C respectively. Western blot was performed to detect the protein level in VSMCs, Alkaline phosphatase (ALP) and Alizarin red staining was used to observe calcium deposition. Dihydroethidium (DHE) staining was used to observe the reactive oxygen species (ROS) production. Here we showed that galectin-3 increased aorta and VSMCs calcification, which was associated with AMPK/TXNIP upregulation and autophagy activation. TXNIP inhibition decreased galectin-3-induced aorta and VSMCs calcification and autophagy activation. 3-MA or Atg5 siRNA decreased galectin-3-induced upregulation of Runx2, BMP2 and OPN. AMPK mediated galectin-3-induced VSMCs osteogenic differentiation. These findings illustrated that TXNIP mediated galectin-3-induced vascular calcification, AMPK and autophagy activation were also associated with this process.

The progression of NTLs after PCI accounts for a significant portion of future adverse cardiac events. The reduction in LDL-C reduces cardiovascular events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes with progression in NTLs. A total of 847 patients with successful PCI were enrolled. Patients with follow-up LDL-C ≥ 1.4 mmol/L or percent reduction <50% compared to baseline were Non-optimal group (n = 793); patients with follow-up LDL-C < 1.4 mmol/L and percent reduction ≥50% compared to baseline were Optimal group (n = 54). Compared to Non-optimal group, Optimal group presented a lower rate of NTL plaque progression (11.11% vs. 23.96%; p = 0.007) and a lower follow-up TC (2.77 ± 0.59 vs. 3.66 ± 0.97; p < 0.001) and LDL-C (1.09 ± 0.26 vs. 2.03 ± 0.71; p < 0.001). The univariate logistic regression analysis revealed that follow-up LDL-C < 1.4 mmol/L and a percent reduction ≥50% from baseline was a protective factor for NTL plaque progression (OR: 0.397; 95%CI: 0.167–0.941; p = 0.036). The multivariate logistic regression model revealed that follow-up LDL-C < 1.4 mmol/L and percent reduction ≥50% was indeed an independent factor associated with a lower rate of plaque progression of NTLs (OR: 0.398; 95% CI: 0.167–0.945; p = 0.037). Therefore, achieving guideline-recommended LDL-C level was associated with a significantly reduced risk of NTL plaque progression.

Vascular smooth muscle cell (VSMC) migration is an important step in the progression and development of vulnerable plaques. Thrombin is involved in both physiological and pathological processes of atherosclerosis. Therefore, the elucidation of the mechanisms underlying thrombin-induced VSMC migration is essential for devising effective treatments aimed at the prevention of plaque instability. In this study, we found that thrombin activated MAPK signaling pathways and increased the expression of galectin-3, which was also a well-known factor in atherosclerosis. Knockdown of galectin-3 by specific small interfering RNA (siRNA) blocked thrombin-induced activation of ERK1/2 and p38 MAPK, but not JNK MAPK. Src/FAK phosphorylation was also shown to be activated by thrombin. FAK autophosphorylation at Y397 was most significantly inhibited by galectin-3 siRNA. Galectin-3 siRNA or specific inhibitor (P38 MAPK inhibitor and ERK1/2 inhibitor) effectively prevented thrombin-induced VSMC migration via reducing paxillin expression. These findings demonstrate, for the first time, that thrombin stimulation of VSMC migration and paxillin expression are regulated by galectin-3, and ERK1/2, p38 MAPK, and Src/FAK signaling pathways are involved in this process. These results are beneficial to clarify the role of galectin-3 in thrombin-induced advanced lesions in atherosclerosis and shed new insights into the regulatory mechanism of VSMC migration in combating plaque rupture.

Objectives. To study the predictive value for coronary artery calcification (CAC) of plasma galectin‐3 and brachial‐ankle pulse wave velocity (BaPWV) in coronary arteriography (CAG) patients. Methods. Patients who received coronary arteriography (CAG) examination were recruited. The level of plasma galectin‐3 was measured by the enzyme‐linked immunosorbent assay. The arterial stiffness was analyzed by BaPWV and ankle‐brachial index (ABI) which were measured using a volume‐plethysmographic device. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of galectin‐3 or BaPWV for coronary artery calcification (CAC). Results. The level of galectin‐3 and BaPWV was significantly higher in CAC patients compared with that in control (p < 0.01). The level of plasma galectin‐3 was positively correlated with BaPWV (r = −0.296, p < 0.01) and negatively correlated with ABI (r = −0.296, p < 0.01). ROC curve analysis revealed that galectin‐3 ≥5.90 ng/ml was the most powerful predictor for CAC with sensitivity of 85.5% and specificity of 83.5%. The area under the curve (AUC) was 0.916. When the level of BaPWV was more than 1909 m/s, the sensitivity and specificity were 61.8% and 69.6%, respectively, for predicting CAC. The AUC was 0.646. Conclusions. The level of plasma galectin‐3 increases significantly in CAC patients compared to control, and its level is related to BaPWV and ABI. Galectin‐3 and BaPWV can be used to predict CAC, and the diagnosis value (sensitivity and specificity) of galectin‐3 for CAC is better than that of BaPWV.

Allicin is an active component of garlic that exerts protective effects against cardiovascular diseases. Vascular contraction and relaxation are the essential capacities of the vascular system to maintain its normal function. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main types of cells that control vascular function. This study was aimed at assessing the effects of allicin on vascular function and exploring its potential regulatory mechanisms. Mass spectrometry analysis was used to identify potential downstream targets of allicin in the artery. A primary culture of mouse VSMCs and ECs was established via enzymatic digestion of the aorta. Small interfering RNA (siRNA) was used to knock down the expression of the target gene, and a vector was used to upregulate specific protein expressions. Protein levels were determined using western blotting. Our results showed that allicin treatment increased both endothelium-dependent and endothelium-independent relaxation in aortic rings. Based on mass spectrometry analysis, we proposed that ATP-binding cassette transporter G1 (ABCG1), ryanodine receptor 2 (RyR2), and peroxisome proliferator-activated receptor γ (PPAR γ) might be the downstream targets of allicin. In ECs, Allicin increased ABCG1 expression and nitric oxide (NO) production, ABCG1 siRNA decreased allicin-induced NO production. RyR2 expression and Ca²⁺ spark were inhibited by allicin in VSMCs; RyR2 overexpression partly reversed the allicin-induced Ca²⁺ spark decrease in VSMCs. PPAR γ siRNA significantly inhibited the effects of allicin in ECs and VSMCs. These results indicated that allicin treatment exerted vasorelaxation effects by increasing ABCG1 expression and NO production in ECs and reducing RyR2 expression and Ca²⁺ spark in VSMCs. The PPAR γ signaling pathway was confirmed to mediate these processes.