Relationship between non-culprit lesion plaque characteristics changes and in-stent neoatherosclerosis formation: 1-year follow-up optical coherence tomography study.

The relationship between the in-stent neoatherosclerosis (ISNA) formation and the plaque's characteristic changes in the non-culprit lesion is unclear. We aim to investigate the plaque characteristics changes at non-culprit lesions between patients with ISNA and without ISNA formation at 1-year follow-up. We retrospectively enrolled patients who had DES implantation in de novo lesion and underwent immediately after stenting and 1-year follow-up optical coherence tomography (OCT) examination. OCT-defined ISNA was defined as the presence of lipid-laden neointima or calcification within the culprit stent with a longitudinal extension of ≥1 mm. Non-culprit lesions were divided into two groups: ISNA group (with ISNA) and non-ISNA group (without ISNA). Plaque characteristics of non-culprit lesions were evaluated at baseline and 1-year follow-up. In total, 89 patients with 89 non-culprit lesions (ISNA: n = 37; non-ISNA: n = 52) were included in the analyses. The lesions in the ISNA group show a smaller minimum lumen area compared to the non-ISNA group at 1-year follow-up (2.57 ± 1.08 mm2 versus 3.20 ± 1.62 mm2, p = 0.044). The lesions of the ISNA group show a significant decrease in minimum lumen area changes percent (-7.25% versus 6.46%, p = 0.039). And there are more lesions with minimum lumen area (64.9% versus 38.5%, p = 0.014) and minimum lumen diameter (64.9% versus 40.4%, p = 0.023) decrease in the ISNA group. Furthermore, the lesions in ISNA group have more plaques with lipid core length increase (25.0% versus 10.0%, p = 0.040), more plaques with FCT decrease (50.0% versus 74.0%, p = 0.027) and less TCFA change to non-TCFA (33.3% versus 87.5%, p = 0.010). The plaque characteristic changes in non-culprit lesions are closely related to ISNA formation. The ISNA formation may accompany by a tardier plaque stabilization process in non-culprit lesions.

Luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation.

Pyroptosis plays an important role in the pathogenesis of numerous infectious, autoimmune, and inflammatory diseases, which makes it a promising target for intervention. In this study, the effect of luteolin on pyroptosis and the underlying mechanism were investigated using the canonical NLRP3 inflammasome in THP-1 macrophages induced by LPS/ATP. The results showed that luteolin exhibited a potent preventive effect on THP-1 macrophage pyroptosis, as evidenced by the increase in cell viability and the decrease in LDH release. Moreover, luteolin was found to significantly reduce the expression of NLRP3, pro-CASP-1 and CASP-1, which are the key components of NLRP3 inflammasome, as well as the expression of N-GSDMD and IL-1ß, and we proved that the inhibition of luteolin on NLRP3 inflammasome activation is ROS-dependent. Furthermore, it was demonstrated that luteolin promoted Nrf2 nuclear translocation, thereby increasing the expression of HO-1 that reduces ROS production, while the anti-pyroptotic effect of luteolin was reversed by a specific Nrf2 inhibitor. Additionally, luteolin inhibited NF-κB p65 phosphorylation and nuclear translocation. In summary, we conclude that luteolin prevents THP-1 macrophage pyroptosis by suppressing ROS production via Nrf2 activation as well as NF-κB inactivation. These results support luteolin as a potential bioactive chemical against pyroptosis-related inflammatory diseases.

Non-culprit plaque characteristics in acute coronary syndrome patients with raised hemoglobinA1c: an intravascular optical coherence tomography study.

BACKGROUND: Raised hemoglobinA1c (HbA1c) is an indicator of pre-diabetes, which is associated with increased risk of coronary artery disease. However, the detailed morphological characteristics of non-culprit plaques in acute coronary syndrome (ACS) patients remain largely unknown. METHODS: A total of 305 non-culprit plaques from 216 ACS patients were analyzed by intravascular optical coherence tomography. These patients were divided into three groups according to the serum glycosylated hemoglobin level: normal HbA1c (< 5.7%), pre-diabetes with raised HbA1c (5.7-6.4%) and diabetes mellitus (DM). RESULTS: Plaques in patients with raised HbA1c had a longer lipid length (17.0 ± 8.3 mm vs. 13.9 ± 7.2 mm, P = 0.004) and greater lipid index (2775.0 ± 1694.0 mm° vs. 1592.1 ± 981.2 mm°, P = 0.001) than those with normal HbA1c but were similar to DM. The prevalence of calcification in patients with raised HbA1c was significantly higher (38.7% vs. 26.3%, P = 0.048) than normal HbA1c but was similar to DM. The percentage of macrophage infiltration in the DM group was higher than that in the normal HbA1c group (20.5% vs. 7.4%, P = 0.005). CONCLUSIONS: Compared to patients with normal HbA1c, the non-culprit plaques in ACS patients with raised HbA1c had more typical vulnerable features but were similar to DM.

Relation of ABO Blood Groups to the Plaque Characteristic of Coronary Atherosclerosis.

The ABO blood types related to morphological characteristics of atherosclerosis plaque are not clear. We aimed to evaluate the relationship between ABO blood groups and the coronary plaque characteristic. We retrospectively identified the target lesions in 392 acute coronary syndrome patients who underwent optical coherence tomography examination before stenting. Subjects were divided into different groups according to different blood types. The fibrous cap thickness was significantly thicker in O type compared with non-O type (0.075 ± 0.033 mm versus 0.061 ± 0.024, p < 0.001). Meanwhile, the incidence of thin-cap fibroatheroma was also significantly higher in O type compared with non-O type (51.0% versus 71.5%, p < 0.001). The O type showed a significantly larger minimum lumen area [1.26 (0.82, 2.13) versus 1.05 (0.67, 1.82), p = 0.020] and minimum lumen diameter [1.03 (0.74, 1.31) versus 0.95 (0.66, 1.25), p = 0.039] compared with non-O type. There were no differences found in incidence of lipid plaque, plaque rupture, and thrombus between different blood type groups even between O type and non-O type group (p > 0.05). The plaques of O type blood group were exhibited more stably compared with non-O type blood group. Moreover, the non-O type blood group have more serious coronary artery stenosis than O type blood group.

Impact of Cigarette Smoking and Smoking Cessation on Stent Changes as Determined by Optical Coherence Tomography After Sirolimus Stent Implantation.

There is debate regarding whether smoking results in microstructural changes after stenting. The aim of this study was to evaluate the microstructural changes after stenting in patients with different smoking statuses. We retrospectively identified 220 sirolimus-eluting stents in 179 patients who underwent follow-up optical coherence tomography examination 12 months after sirolimus stenting. Subjects were classified as current smokers (CS, n = 31), smoking cessation ≤1 year (n = 36), smoking cessation >1 year (SC > 1Y, n = 27), and never smokers (NS, n = 85). The neointimal hyperplasia (NIH) area was larger in CS than in NS (1.04 ± 0.72 mm2 vs 0.96 ± 0.68 mm2; p = 0.04). The incidence of lipid-laden neointima was lower in SC > 1Y patients (1.6%) than in all other patients (NS: 3.9%, p = 0.002; CS: 3.0%, p = 0.073; SC1Y: 5.0%, p <0.001). Smoking cessation level was negatively correlated with NIH (B = -0.154; 95% confidential interval -0.187, -0.121; p <0.001) and independently associated with the presence of homogeneous neointima (odds ratio: 1.414; 95% confidential interval 1.145, 1.745; p = 0.001). The incidence of malapposed struts was higher in CS than in NS (3.2% vs 1.6%; p = 0.004). However, smoking cessation patients showed a decreased trend in the incidence of malapposed struts (p = 0.0003). In conclusion, continued smoking increases NIH and the incidence of malapposed struts. However, smoking cessation slows down NIH progression and decreases the incidence of malapposed struts. Smoking cessation promotes vascular healing after stenting.

Structural study on the interactions of oxaliplatin and linear DNA.

Damage to cellular DNA is believed to determine the cytotoxicity of oxaliplatin. However, high resolution structures formed by oxaliplatin and different linear DNA remain unclear. This study characterized, the key structures of different linear DNA in the platination process by UV absorption spectra and atomic force microscopy (AFM). Bathochromic shift and hyperchromicity in UV spectra after addition of oxaliplatin revealed that it can disrupt base stacking of DNA in the platination process. AFM results of different linear DNA indicated that, the platination process can induce DNA change from an extended conformation to the network structure with many kinks and finally to the compact particles, or toroids with increasing the incubation time. All AFM results confirmed that, platination of different linear DNA by oxaliplatin is a time depended process. The present AFM results provide, structural evidence about the interactions between oxaliplatin and different linear DNA containing multiple targets. SCANNING 38:880-888, 2016. © 2016 Wiley Periodicals, Inc.

Localization of in-stent neoatherosclerosis in relation to curvatures and bifurcations after stenting.

BACKGROUND: In-stent neoatherosclerosis (ISNA) is a final common pathway of late-stent failure. However, distribution of ISNA has been little reported. This study was to evaluate the localization of ISNA in relation to curvatures and bifurcations after stent implantation using optical coherence tomography (OCT). METHODS: We retrospectively selected patients who underwent OCT examination ≥12 months after stent (sirolimus-eluting stents, SES) implantation. A stent curvature was defined if the angulation of the stent segment was >29°. Distribution of ISNA in relation to stent curvature and bifurcation was evaluated. RESULTS: Totally, 331 patients were enrolled. The mean follow-up time was 15 months. Forty-one (12.3%) patients were found with ISNA. OCT results showed that stents with ISNA had thicker neointima (mean neointima thickness: 0.16 vs. 0.08 mm, P<0.001) compared to patients without ISNA. Segments with angulation >29° had a higher prevalence of ISNA compared with to angulation ≤29° [18 (18.4%) vs. 23 (9.9%), P=0.032]. ISNA was more frequently located at the "inner curvature" than the "outer curvature" (77.8% vs. 22.2%, P=0.018). If ISNA occurred in a branch, it was more often on the opposite side of the branch compared with the same side of the branch [21 (77.8%) vs. 6 (22.2%), P=0.004]. CONCLUSIONS: Localization of ISNA is related to vessel curvatures and bifurcations. ISNA occurs more often on the inner curvature and the opposite side of the branch.

Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway.

Chimaphilin, 2,7-dimethyl-1,4-naphthoquinone, is extracted from pyrola [Passiflora incarnata Fisch.]. In this study, the anticancer activity and underlying mechanisms of chimaphilin toward human breast cancer MCF-7 cells are firstly investigated. Chimaphilin could inhibit the viability of MCF-7 cells in a concentration-dependent manner, and the IC50 value was 43.30µM for 24h. Chimaphilin markedly induced apoptosis through the investigation of characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining. Flow cytometry assay revealed that chimaphilin triggered a significant generation of ROS and disruption of mitochondrial membrane potential. Additionally, western blotting assay showed that chimaphilin suppressed Bcl-2 level and enhanced Bad level, then activated caspase-9 and caspase-3, and further activated the poly ADP-ribose polymerase (PARP), finally induced cell apoptosis involving the mitochondrial pathway. Furthermore, free radical scavengers N-acetyl-L-cysteine (NAC) pretreatment test testified that chimaphilin could increase the generation of ROS, then induce cell apoptosis. In general, the present results demonstrated that chimaphilin induced apoptosis in human breast cancer MCF-7 cells via a ROS-mediated mitochondrial pathway.