Lumbar disc herniation is an independent predictor of plaque burden in the patients with unstable angina.

Objective: Assessing the impact of lumbar disc herniation (LDH) on the plaque burden of coronary atherosclerosis is our objective. Methods: In this study, a total of 212 patients (age 46-80 years) with unstable angina (UA) who underwent coronary angiography (CAG) in our hospital from January 2018 to July 2022 due to UA were included. Patients were divided into LDH group (n = 106) and no LDH group (n = 106). Gensini scores were calculated to assess the plaque burden of coronary. Logistic analysis was used to examine potential risk variables linked to the Gensini score. The association between lumbar disc lesions grading and coronary plaque burden was analysed by Spearman's correlation test. LDH patients with higher plaque burden (n = 56) were further divided into evolocumab treatment group (n = 28) and conventional treatment group (n = 28). Cox regression analysis were performed. Results: Patients with LDH had higher Gensini scores (P < 0.01) and triglyceride (TG) levels (P = 0.04), but HDL-C (P = 0.01) levels were lower. LDH was found to be an independent risk factor for higher Gensini scores (OR = 2.38, P < 0.01) by logistic analysis. The Spearman's correlation test suggested that the degree of lumbar disc lesions was related to the Gensini score and the level of blood lipid. Cox regression analysis showed that evolocumab treatment could significantly reduce the composite MACE events (cardiac death, nonfatal myocardial infarction, nonfatal stroke, and readmission due to angina) (HR = 0.26, P = 0.04) in higher coronary plaque burden patients. Conclusion: LDH is an independent risk factor for the higher coronary plaque burden. Evolocumab treatment significantly reduced the occurrence of cardiovascular events in LDH patients with higher plaque burden. Additionally, our data indicate that LDH is associated with increased blood lipid, which may contribute to the development of plaque burden.

Melatonin attenuates AFB1-induced cardiotoxicity via the NLRP3 signalling pathway.

OBJECTIVE: This study was conducted to investigate the protective effect of melatonin against aflatoxin B1 (AFB1) cardiotoxicity by evaluating NOD-like receptor family pyrin domain containing protein 3 (NLRP3) signalling. METHODS: Four groups of five rats each were assessed: control group (vehicle only), two AFB1 (0.15 and 0.3 mg/kg)-treated groups, and a combined AFB1 (0.3 mg/kg) plus melatonin (5 mg/kg)-treated group. After 6 weeks of once-daily intragastric treatment, cardiac pathologic changes were observed under optical microscopy, and oxidative/antioxidative parameters were measured in myocardial homogenate. Cardiac tissue expression of NLRP3 and other important inflammasome components was also analysed. RESULTS: Compared with controls, increasing concentrations of AFB1 were associated with increased oxidative stress and caused myocardial structure damage. In addition, AFB1 dose-dependently activated the NLRP3 signalling pathway. All these indices were significantly ameliorated by combined AFB1 plus melatonin treatment versus high-dose AFB1 alone. CONCLUSION: Melatonin may reduce NLRP3 inflammasome activation by inhibiting oxidative stress and thus protect against injury from AFB1-induced myocardial toxicity.

The effect of olmesartan on aortic intimal thickening after balloon injury through Apelin/APJ.

PURPOSE: Restenosis is the main complication after percutaneous coronary intervention. The proliferation of new intima contributes to the process. In this study, we aimed to explore the effect of olmesartan on intimal thickening after balloon injury and possible mechanism. METHODS: Aortic endothelial denudation model was made by a 2F balloon catheter. Thirty-six rats were randomly allocated into three groups: Control (n = 12) Surgery (n = 12, received vascular balloon injury) and Olmesartan (n = 12, received 3 mg.kg-1.d-1olmesartan after injury). Fourteen and 28 days after injury, HE staining was used to assess the aortic endothelial injury. Radioimmunological method was used to examine the level of angiotensin II (Ang II). Western blotting and reverse transcription polymerse chain reaction (RT-PCR) were employed to detect the protein and mRNA level of Apelin/APJ. RESULTS: After vascular balloon injury, the proliferation of vascular smooth muscle cells and the intimal thickening were increased. The mRNA and protein level of Ang II, AT1, Apelin and APJ mRNA were promoted by vascular balloon injury. Olmesartan decreased the proliferation of vascular smooth muscle cells and the intimal thickening. Olmesartan decreased the expression of Ang II and AT1, but further increased the expression of Apelin and APJ. Balloon injury also induced the activation of Extracellular signal-regulated kinase (ERK) signaling and olmesartan decreased the effect. CONCLUSION: Olmesartan inhibits the intimal thickening through activating Apelin/APJ and inhibiting AngII-AT1 and ERK pathway.

Determinants of angiographic thrombus burden and impact of thrombus aspiration on outcome in young patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We aimed to investigate the determinants of thrombus burden (TB) and the impact of thrombus aspiration (TA) on outcome in young adults with ST segment elevation myocardial infarction (STEMI). BACKGROUND: The determinants of TB in young STEMI patients are not fully understood now. METHODS: The 182 young (age ≤ 45 years) STEMI patients, who underwent coronary angiography and percutaneous coronary intervention (PCI) in our hospital from January 2013 to September 2016, were included. Angiographic TB and impact of TA on major adverse cardiac events (MACEs) were evaluated. Median clinical follow-up period was 875 (641-1,052) days. RESULTS: All patients were male, mean age was 40 ± 5 years. High thrombus burden (HTB) was evidenced in 100 (54.9%) patients. TA was performed in 62 out 100 (62%) patients with high TB (HTB) during PCI. The prevalence of hypertension was significantly higher in the HTB group than in the low thrombus burden (LTB) group (75 vs. 17%, P < 0.001). The proportion of smoking, alcohol consumption, and family history of premature coronary artery disease were similar between HTB and LTB groups. During follow-up, 2 patients died and 31 patients underwent repeat PCI. MACE rate was significantly higher in the HTB group than in the LTB group (24.0 vs. 9.8%, P = 0.012) and significantly lower in HTB patients with TA than HTB patients without TA (14.5 vs. 39.5%, P = 0.018). CONCLUSIONS: Hypertension is an independent determinant of HTB and TA could be considered as an effective therapeutic option in young male STEMI patients with HTB.

Hypertension Is an Independent Predictor of Multivessel Coronary Artery Disease in Young Adults with Acute Coronary Syndrome.

BACKGROUND: Risk factors of multivessel coronary artery disease (CAD) among young acute coronary syndrome (ACS) patients remain elusive now. METHODS: This retrospective study analyzed data from 187 consecutive young (age ≤45 years) ACS patients (75 STEMI, 30 NSTEMI, and 72 unstable angina) hospitalized in our hospital from January 2012 to December 2016. Thirty-six young male patients with normal coronary angiography (CAG) findings (no-CAD), who underwent CAG due to suspected chest pain in this period, served as control group. There were 83 patients with single-vessel disease (SVD) and 104 patients with multiple-vessel disease (MVD) among ACS patients. Patients were followed up for a mean of 267±124 days by clinical visit or telephone calls. RESULTS: All included patients were male. Prevalence of hypertension (57.2% vs. 30.6%, p=0.002) and smoking (70.6% vs. 52.8%, p=0.049) was significantly higher in ACS patients than in no-CAD patients. Prevalence of hypertension (72.1% vs. 38.6%, p<0.001) and body mass index (BMI) were significantly higher in MVD group than in SVD group. Multivariable analysis revealed that hypertension was an independent risk factor for MVD after adjustment for age, gender, BMI, smoking, family history of premature CAD, hyperlipidemia, left ventricular ejection fraction, and brain natriuretic peptide (odds ratio=3.71, 95% confidence interval=1.84-7.46, p<0.001). Rate of major adverse cardiovascular events (MACE) during follow-up (20.2% vs. 4.8%) was significantly higher in MVD group compared with SVD group. CONCLUSIONS: Hypertension is an independent predictor of MVD and MVD is associated with increased MACE rate compared to SVD in young ACS patients during the short-term follow-up.

Thrombus Aspiration for ST-Segment-Elevation Myocardial Infarction in Modern Era: Still an Issue of Debate?

The role of manual thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) for acute ST-segment-elevation myocardial infarction has been a matter of intense research and debate now. Although recent randomized controlled clinical trials (notably TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia] and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) do not supply evidence supporting the routine use of TA in patients with ST-segment-elevation myocardial infarction, manual TA remains a therapeutic option for interventional cardiologists when treating patients with substantial thrombus burden during PPCI. It remains unknown whether patients might actually benefit from TA applied in a more selective manner depending on the thrombus burden during PPCI, instead of routine application. In this review, we summarize current knowledge on the instruments used in the TA procedure, positive as well as negative clinical effects of TA during PPCI, and analyze the potential reasons for observed effects, in an effort to help the clinical decision making by physicians for the use of TA in individual ST-segment-elevation myocardial infarction patients during PPCI.

Acute Coronary Stent Thrombosis in Modern Era: Etiology, Treatment, and Prognosis.

Acute stent thrombosis (AST) is a rare but life-threatening complication of coronary artery stenting. AST remains a challenging task for cardiologists, despite the application of modern procedural techniques and dual-antiplatelet therapy strategies as well as improved understanding of the underlying pathophysiology. This review focuses on the prevalence, risk factors, prognosis, multiple potential underlying pathogenesis, knowledge gaps, and recommends diagnosis and individualized management strategies of AST.

Assessment of aflatoxin B1 myocardial toxicity in rats: mitochondrial damage and cellular apoptosis in cardiomyocytes induced by aflatoxin B1.

Objective The number of deaths from heart disease is increasing worldwide. Aflatoxin B1 (AFB1), a toxin produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is frequently detected in improperly processed/stored human food products. While AFB1 hepatotoxicity and carcinogenic properties have been well addressed, its myocardial toxicity is poorly documented. This study aimed to investigate myocardial toxic activity of AFB1. Methods Ten rats were fed with AFB1 at a dose that did not result in acute toxic reactions for 30 days and 10 vehicle-fed rats served as controls. Transmission electron microscopy was used to assess mitochondrial damage in cardiomyocytes. The terminal deoxynucleotidyl transferase-mediated UTP nick-end labelling assay was performed to detect apoptosis of cardiomyocytes. Western blotting was performed to measure apoptotic proteins (i.e., active caspase-3, Bax, and Bcl-2) in heart tissue. Results AFB1 treatment resulted in mitochondrial membrane disruption and disorganization of cristae, which are indicators of mitochondrial damage. Myocardial cell apoptosis was significantly higher after AFB1 treatment (22.07% ± 3.29%) compared with controls (6.27% ± 2.78%, P < 0.05). AFB1 treatment enhanced expression of active caspase-3, Bax, and Bcl-2 in cardiac tissue. Conclusion Various adverse effects are exerted by AFB1 on the heart, indicating AFB1 myocardial toxicity.

Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.

Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB.

BACKGROUND/AIMS: Tanshinone IIA (Tan IIA) is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan IIA on expression of adhesion molecules in tumor necrosis factor-α (TNF-α)-induced endothelial progenitor cells (EPCs). METHODS: EPCs were pretreated with Tan IIA and stimulated with TNF-α. Mononuclear cell (MNC) adhesion assay was performed to assess the effects of Tan IIA on TNF-α-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1)/intracellular adhesion molecule-1 (ICAM-1) and activation of Nuclear factor κB (NF-κB) signaling pathway were measured. RESULTS: The results showed that the adhesion of MNCs to TNF-α-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-α, which were reduced by Tan IIA. TNF-α increased the amount of phosphorylation of NF-κB, IκB-α and IKKα/ß in cytosolic fractions and NF-κB p65 in nucleus, while Tan IIA reduced its amount. CONCLUSION: This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-α-induced NF-κB activation and IκB-α phosphorylation by the inhibition of IKKα/ß pathway in EPCs.

Pioglitazone alleviates inflammation in diabetic mice fed a high-fat diet via inhibiting advanced glycation end-product-induced classical macrophage activation.

Classically activated macrophages (M1) are associated with inflammation in diabetic patients. Inflammation is a known risk factor in diabetes. The present study tested the hypothesis that pioglitazone (PIO) alleviates inflammation in diabetic mice fed a high-fat diet by inhibiting advanced glycation end-product (AGE)-induced classical macrophage activation. It was found that AGE treatment promoted the transcription of pro-inflammatory molecules and M1 surface markers, whereas PIO increased the expression of anti-inflammatory genes and decreased the expression of pro-inflammatory mediators in bone marrow-derived macrophages (BMDMs) in a dose-dependent manner. Furthermore, pretreatment with PIO abrogated the effects of AGE on pro-inflammatory markers and partly inhibited AGE-induced nuclear factor-κB (NF-κB) activation. PIO treatment partly reduced the inflammatory phenotype in diabetic ApoE(-/-) mice, and significantly reduced NF-κB activation in plaques. Therefore, we conclude that PIO blocks classical activation of macrophages and attenuates inflammation in mouse models of diabetes.

Novel hydroxybutyl chitosan nanoparticles for siRNA delivery targeting tissue factor inhibits proliferation and induces apoptosis in human vascular smooth muscle cells.

Chitosan, a polysaccharide isolated from shrimp and other crustacean shells, has been widely investigated for DNA and siRNA delivery. Despite substantial effort having been made to improve chitosan as a non­viral gene delivery vector, the application is severely limited by its poor solubility under physiological conditions. Hydroxybutyl chitosan (HBC), a modified chitosan, is soluble under neutral conditions. Tissue factor (TF) is involved in the pathogenesis of cardiovascular diseases by promoting thrombus formation and inducing the migration and proliferation of vascular smooth muscle cells. Targeting TF is an attractive therapeutic strategy for cardiovascular diseases. In the present study, the use of HBC for the transfer of TF­siRNAs into human umbilical vein smooth muscle cells (HUVSMCs) was investigated, and the effects of TF knockdown on cell proliferation and apoptosis were examined. HBC/siRNA nanoparticles were produced by mixing HBC and siRNA solutions with the assistance of tripolyphosphate buffer. The transfection efficiency with these nanoparticles was 74±2.5%, which was determined using a fluorescence­labeled siRNA under fluorescence microscopy. The delivery of HBC/TF­siRNA resulted in reductions in the production of cellular and soluble TF protein in HUVMSCs, which were measured using western blotting and enzyme­linked immunosorbent assay, respectively. TF knockdown led to inhibited cell proliferation, as assessed using a Cell Counting Kit­8 assay, and increased cell apoptosis, determined using Annexin V­fluorescein isothiocyanate staining. These findings suggested that HBC may be a promising vector for siRNA delivery, and that in vivo HBC/siRNA nanoparticle delivery targeting TF may be a potential option for the treatment of cardiovascular diseases, which warrants further investigation.

Readmission rate after coronary artery bypass grafting versus percutaneous coronary intervention for unprotected left main coronary artery narrowing.

Many studies have reported comparable risk of hard end points between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) stenosis. However, there are limited data regarding the morbidity associated with ULMCA revascularization. This study sought to compare the cause and risk of readmissions after PCI and CABG for ULMCA stenosis. We evaluated the unadjusted and adjusted risk of readmissions in 1,352 patients (783 PCI treated and 569 CABG treated) who were consecutively enrolled in a multicenter registry of patients with ULMCA stenosis, named the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease trial. Overall, 206 PCI-treated patients (26.3%) experienced at least 1 readmission after the index procedure during 48.7 ± 16.0 months of follow-up compared with 84 CABG-treated patients (14.8%, p <0.001). The most frequent causes of readmission were repeat revascularization after PCI (41%) and noncardiac readmissions after CABG (48%). Through repeated events analysis, PCI was associated with more frequent readmissions than CABG (hazard ratio 2.037, 95% confidence interval 1.542 to 2.692, p <0.001), being an independent predictor of readmission (hazard ratio 1.820, 95% confidence interval 1.420 to 2.331, p <0.001). Except for the acute period, defined as the first 3 months, when there was no significant difference in readmission rate, a higher readmission rate after PCI was consistently observed over the remainder of the follow-up period. In conclusion, PCI was shown to be associated with a higher risk of readmission than CABG in treating ULMCA disease. This higher risk was attributable to more frequent revascularization in the PCI group.

Changes in proteomics profile during maturation of marrow-derived dendritic cells treated with oxidized low-density lipoprotein.

Increasing evidence suggests that dendritic cells (DCs) and oxidized low-density lipoprotein (ox-LDL) participate in atherosclerosis. However, few data on the molecular mechanisms of this process are available. To address this question, we used iTRAQ labeling followed by LC-MS/MS analysis to identify many proteins that changed markedly during the maturation of dendritic cells stimulated with ox-LDL. Among a total of 781 identified proteins, 93 were upregulated and 100 were downregulated. The major and significant changes in upregulated proteins were that ox-LDL not only affected the levels of intracellular cathepsins G, Z, D and S, but also significantly enhanced cathepsin S secretion by the treated cells. Our results may provide clues for a more comprehensive understanding the pathogenesis of atherosclerosis.

MicroRNA-29a regulates pro-inflammatory cytokine secretion and scavenger receptor expression by targeting LPL in oxLDL-stimulated dendritic cells.

There is increasing evidence that microRNAs (miRNAs) play important roles in cell proliferation, apoptosis and differentiation that accompany inflammatory responses. However, whether microRNAs are associated with DC immuno-inflammatory responses with oxidized low density lipoprotein (oxLDL) stimulation is not yet known. Our study aims to explore the link of miRNAs with lipid-overload and immuno-inflammatory mechanism for atherosclerosis. In DCs transfected with microRNA-29a mimics or inhibitors, we showed that microRNA-29a plays an important role in proinflammatory cytokine secretion and scavenger receptor expression upon oxLDL-treatment. Furthermore, we suggest an additional explanation for the mechanism of microRNA-29a regulation of its functional target, lipoprotein lipase. We conclude that microRNA-29a could regulate pro-inflammatory cytokine secretion and scavenger receptor expression by targeting lipoprotein lipase in oxLDL-stimulated dendritic cells.

Ox-LDL can enhance the interaction of mice natural killer cells and dendritic cells via the CD48-2B4 pathway.

The importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well documented; however, limited information on NK/DC interaction during atherosclerosis is available. Inflammation plays an important role in the development of atherosclerosis, and oxidized low-density lipoprotein (ox-LDL) is believed to play a critical role in the development and progression of atherosclerosis. In this study, we developed a NK/DC coculture system to examine the role of ox-LDL in modulating the interaction of mice NK cells and DCs. Fresh NK cells were cocultured with DCs in the absence or presence of ox-LDL. We examined the cytokines released during the interaction. This report provides the first evidence of an enhancement effect by ox-LDL on the NK/DC crosstalk. Notably, we found that ox-LDL significantly promoted the interaction of NK cells and DCs via CD48-2B4 contact-dependent mechanisms. These findings highlight the importance of NK/DCs crosstalk in atherosclerosis and provide new information about the possible mechanisms of atherosclerosis.

MicroRNA-146a regulates the maturation process and pro-inflammatory cytokine secretion by targeting CD40L in oxLDL-stimulated dendritic cells.

There is increasing evidence that microRNAs (miRNAs) play important roles in cell proliferation, apoptosis and differentiation that accompany inflammatory responses. However, whether miRNAs are associated with dendritic cell (DC) immuno-inflammatory responses to oxidized low density lipoprotein (oxLDL) stimulation is yet unknown. Our study aims to explore the link of miRNA to lipid-overload and the immuno-inflammatory mechanism for atherosclerosis. Human primary monocyte-derived DCs were transfected with miR-146a mimics and inhibitor, and then stimulated by oxLDL. For the flow cytometric analysis of the DC immunophenotype, supernatants were collected to determine inflammatory chemokine markers. Our study clearly revealed that miRNA-146a regulates the maturation process and pro-inflammatory cytokine secretion in DCs by targeting CD40L in ox-LDL-stimulated DCs.