OBJECTIVES: To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. METHODS: Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. RESULTS: The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). CONCLUSIONS In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.
Male ; Animals ; Mice ; Mucocutaneous Lymph Node Syndrome/pathology* ; Coronary Vessels/pathology* ; NF-kappa B ; Caspase 3/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Chitinase-3-Like Protein 1 ; von Willebrand Factor/metabolism* ; Mice, Inbred C57BL ; Cadherins

OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).

METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).

RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).

CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood

Current guidelines recommend that coronary artery calcium (CAC) screening should only be used for intermediate risk groups (Framingham risk score [FRS] of 10%-20%). The CAC distributions and coronary artery disease (CAD) prevalence in various FRS strata were determined. The benefit to lower risk populations of CAC score-based screening was also assessed. In total, 1,854 participants (aged 40-79 years) without history of CAD, stroke, or diabetes were enrolled. CAC scores of > 0, ≥ 100, and ≥ 300 were present in 33.8%, 8.2%, and 2.9% of the participants, respectively. The CAC scores rose significantly as the FRS grew more severe (P < 0.01). The total CAD prevalence was 6.1%. The occult CAD prevalence in the FRS ≤ 5%, 6%-10%, 11%-20%, and > 20% strata were 3.4%, 6.7%, 9.0%, and 11.6% (P < 0.001). In multivariate logistic regression analysis adjusting, not only the intermediate and high risk groups but also the low risk (FRS 6%-10%) group had significantly increased odds ratio for occult CAD compared to the very low-risk (FRS ≤ 5%) group (1.89 [95% confidence interval, CI, 1.09-3.29] in FRS 6%-10%; 2.48 [95% CI, 1.47-4.20] in FRS 11%-20%; and 3.10 [95% CI, 1.75-5.47] in FRS > 20%; P < 0.05). In conclusion, the yield of screening for significant CAC and occult CAD is low in the very low risk population but it rises in low and intermediate risk populations.
Aged ; Calcium/*analysis ; Coronary Artery Disease/*diagnosis/epidemiology/pathology ; Coronary Vessels/*chemistry/diagnostic imaging/metabolism ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Prevalence ; Risk Factors ; Severity of Illness Index ; Tomography, X-Ray Computed

OBJECTIVETo examine the effect of H2S donor, sodium hydrosulfide (NaHS), on ET-1 level in plasma and aorta in rats with atherosclerosis (AS).

METHODThirty male rats, weighting 200-220 g, were randomly divided into AS, AS+NaHS and control groups, n = 10 in each group.Rats were given a single dose of vitamin D3 (700 000 U/kg) in the first three days and fed with a high-cholesterol diet for 8 weeks to induce AS. Rats in AS+NaHS group were intraperitoneally injected with an H2S donor NaHS, at a dose of 56 µmol/(kg·d) for 8 weeks. At the end of the experiment for 8 weeks, all the rats were sacrificed. The plasma was collected and the aorta and coronary tissues were isolated. The atherosclerotic lesions in both aorta and coronary arteries were detected using oil red O method. H2S concentration in plasma was determined with sulfide-sensitive electrode method. ET-1 levels in plasma and aorta were calculated by radioimmunoassay kit and the localization of ET-1 in the aorta was detected by immunohistochemistry. Plasma nitric oxide synthase (NOS), endothelial NOS (eNOS), inducible NOS (iNOS) were detected with colorimetry.

RESULTAS plaque area in root of aorta of rats in AS group, AS+NaHS group and control group were (11.6±3.3)%, (1.6±1.1)%, (0.0±0.1)% respectively. The difference in AS plaque area in root of aorta among the three groups was statistically significant (F=97.675, P < 0.05). AS plaque area in coronary artery of rats in AS group, AS+NaHS group and control group were (21.4±5.7)%, (4.8±2.5)%, (0.0±0.0)% respectively. The difference in AS plaque area in coronary artery among the three groups was statistically significant (F=97.519, P < 0.05). Plasma H2S level in rats of AS group ((22.0±3.1) µmol/L) was significantly lower than that of control group ((27.9±1.0) µmol/L) and AS+NaHS group ((33.3±6.2) µmol/L, all P < 0.05). Compared with control group ((70.0±10.7) ng/L), plasma ET-1 in rats of AS group ((89.6±14.2) ng/L) and AS+NaHS group ((93.1±15.5) ng/L, P both < 0.05) were increased. However, there was no significant difference in plasma ET-1 content in rats between AS+NaHS group and AS group (P > 0.05). Compared with control group ((3.8±1.2) ng/g), ET-1 content in aorta in rats of AS group ((11.9±4.9) ng/g) and AS+NaHS group ((8.2±2.5) ng/g, both P < 0.05) were increased, and ET-1 content in aorta in rats of AS+NaHS group was decreased compared with AS group (P < 0.05). Immunochemistry results showed that ET expression in cytoplasm in aortic endothelial cells in rats of AS group was strengthened, while ET expression in rats of control group and AS+NaHS group was weak. NOS activity of rats in control group, AS group and AS+NaHS group was (25.4±5.6), (51.8±10.0) and (27.6±6.5) U/ml, eNOS activity (15.3±6.2), (4.5±2.7) and (8.7±3.9) U/ml, and iNOS activity (9.9±4.0), (47.3±10.7) and (19.0±5.2) U/ml, respectively.Differences among the three groups were statistically significant (NOS activity: F=37.231, P < 0.05, eNOS activity: F=14.600, P < 0.05, and iNOS activity: F=72.131, P < 0.05).

CONCLUSIONH2S donor NaHS reduced the AS plaque in AS rats. The mechanisms might involve the protective effect of H2S on the vascular endothelial cell, decreasing ET-1 production in aortal endothelium of atherosclerotic rats.

Animals ; Aorta ; metabolism ; pathology ; Atherosclerosis ; metabolism ; pathology ; Coronary Vessels ; pathology ; Disease Models, Animal ; Endothelin-1 ; blood ; metabolism ; Hydrogen Sulfide ; pharmacology ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Random Allocation ; Rats ; Sulfides ; pharmacology

OBJECTIVETo establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles (MVs) from myocardial ischemic preconditioning (IPC) treated rats (IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion (I/R) injury in rats.

METHODSMyocardial IPC was elicited by three.cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending (LAD) coronary artery. Platelet-free plasma (PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFR PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 µm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure (MAP), heart rate (HR) and ST-segment of electro-cardiogram (ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin (HE) staining. The activity of plasma lactate dehydrogenase (LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining.

RESULTSTotal IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs (LMVs) and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (<1 Vm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats (P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR (P<0.01), decreased ST-segment and LDH activity (P < 0.05, P < 0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment (P < 0.01).

CONCLUSIONThe method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.

Animals ; Cell-Derived Microparticles ; metabolism ; Coronary Vessels ; pathology ; Flow Cytometry ; Heart Rate ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; Myocardium ; pathology ; Phenotype ; Rats

BACKGROUNDLittle is known about the influence of metabolic syndrome (MetS) on coronary artery calcification (CAC) in China. In this article, we aimed to explore the distribution of CAC in populations with and without MetS, and estimate the influence of MetS and its components on CAC in a community-based population of Beijing.

METHODSA total of 1647 local residents of Beijing, age 40-77 years, were recruited for a cardiovascular risk factors survey and were determined fasting plasma glucose (FPG), blood lipids, and 64 multi-detector computed tomography (64-MDCT) coronary artery calcium score (CACS) measurement (Agatston scoring). The distribution of CAC was described, and the influence of MetS components on CAC was evaluated.

RESULTSIn this population, the prevalence and extent of CAC increased with increasing age and both were higher in MetS subjects compared to nonMetS subjects (all P < 0.05), with the exception of those older than 65 years old. The risk of CAC increased with increasing numbers of MetS components, and the odds ratios for predicting positive CAC in subjects with 1, 2, 3, and = 4 MetS components were 1.60, 1.84, 2.12, and 3.12, respectively (all P < 0.05). Elevated blood pressure, elevated FPG, elevated triglycerides, and overweight increased the risk of CAC, yielding odds ratios of 2.64, 1.67, 1.32, and 1.37, respectively (all P < 0.05).

CONCLUSIONSIn the Beijing community-based population, MetS increases the risk of CAC. The risk of CAC increases with increasing numbers of MetS components. Not only the number, but also the variety of risk factors for MetS is correlated with the risk of CAC. Elevated blood pressure, hyperglycemia, hypertriglyceridemia and overweight increase the risk of CAC.

Adult ; Aged ; China ; epidemiology ; Coronary Artery Disease ; epidemiology ; metabolism ; pathology ; Coronary Vessels ; metabolism ; pathology ; Female ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; metabolism ; pathology ; Middle Aged ; Risk Factors

BACKGROUNDInflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein (CRP) is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 (MMP-9) is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques.

METHODSPatients with newly diagnosed unstable angina pectoris from clinical presentation and ECG, who were undergoing coronary angiography from April 2007 to April 2009, were included in this study. A total of 170 subjects were enrolled in the study. Before angiography, the baseline clinical data (mainly including conventional risk factors) was collected. These patients were divided into two groups, a non-plaque group (G1) which included 55 patients with no significant stenosis or less than 20% stenosis in at least one of the major coronary artery branches, and a plaque group (G2) which included 115 patients with at least one of the major coronary artery branches unstable angina pectoris with at least 50% stenosis of one major coronary artery. The patients presenting with calcified nodules of a major coronary artery were excluded from this study. We examined the serum levels of MMP-9 for all cases by multi-effect enzyme-linked immunosorbent assay.

RESULTSThere was a significant difference in the serum levels of MMP-9 between the two groups (P < 0.001). The percentage of patients with hypertension, diabetes and current smokers were significantly different between the two groups (P = 0.034, P = 0.031, and P = 0.044 respectively). The univariate Logistic regression analyses of risk factors showed that smoking was the main risk factor for angina in the non-plaque group with the OR being 1.95 (95%CI 1.02 - 3.75). Hypertension, diabetes mellitus were negatively related with the occurrence of angina in the non-plaque group with the ORs being 0.50, and 0.36, respectively (95%CI 0.26 - 0.96 and 0.14 - 0.94). The MMP-9 level was negatively related to the occurrence of angina in the non-plaque group with an OR of 0.59 (95%CI 0.47 - 0.81).

CONCLUSIONSThere is a significantly difference in MMP-9 levels between the plaque and non-plaque groups. Current smoking has a significant influence on unstable angina patients without documented plaques. The serum MMP-9 level may be a significant biomarker which can help differentiate patients with unstable angina with plaques from those with unstable angina but without plaques.

Aged ; Angina, Unstable ; blood ; metabolism ; physiopathology ; C-Reactive Protein ; metabolism ; Coronary Angiography ; Coronary Artery Disease ; blood ; metabolism ; physiopathology ; Coronary Vessels ; metabolism ; pathology ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Smoking ; adverse effects

OBJECTIVETo study the safety and efficacy of control-releasing arsenic trioxide (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen (CIII) in canine coronary artery post-stent model.

METHODSTwenty-four experimental canines were equally divided into 4 groups, the three tested groups were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4 microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX), while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology, and changes of SMC and C III expressions were detected using immunohistochemical analysis.

RESULTSSubintimal hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups. Positive expression of SMC and CIII in the tested groups, especial in the high dose As2O3 group, was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower, but the mean luminal diameter was larger in the three tested groups than that in the control group (P < 0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P < 0.01), but that between high dose vs. median dose was insignificant (P > 0.05).

CONCLUSIONControl-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo-genesis of intimal hyperplasia.

Animals ; Arsenicals ; administration & dosage ; pharmacology ; Collagen Type III ; metabolism ; Coronary Restenosis ; etiology ; prevention & control ; Coronary Vessels ; metabolism ; pathology ; Dogs ; Drug-Eluting Stents ; Female ; Implants, Experimental ; Male ; Muscle, Smooth, Vascular ; drug effects ; metabolism ; pathology ; Oxides ; administration & dosage ; pharmacology ; Tunica Intima ; drug effects ; pathology

OBJECTIVETo examine the relationship between reduction of serum fetuin A and coronary artery calcification (CAC) in patients starting hemodialysis.

METHODSTwenty-nine patients on chronic hemodialysis (duration of hemodialysis less than 6 months) were enrolled in this study. Serum fetuin A and such potential CAC-related risk factors as C-reactive protein (CRP), Ca, P, iPTH, body mass index (BMI) were examined. CAC was detected by multislice spiral CT scan (MSCT) and quantified by the modified Agaston's scoring system. All the 29 patients were followed up for 18 months to appraise the cardiovascular events defined as cardiac failure, angina pectoris or myocardial infarction.

RESULTSEleven patients (78.57%) were found to have CAC as detected by MSCT in low serum fetuin A (below the average serum concentration of 0.71 g/L) group, a rate significantly higher than that in high serum fetuin A group (7 patients, 46.67%, P<0.05). Serum fetuin A in these 29 patients was related with CAC score (Pearson correlation coefficient of -0.734, P=0.001) and stepwise regression analysis indicated that serum fetuin A (standardized beta=-0.568, P=0.003) and age (standardized beta=0.416, P=0.019) were independently correlated to CAC. Such factors as CRP, Ca, P, iPTH, Chol, TG, HDL-C, LDL-C, BMI and blood pressure were excluded from the regression equation. Reduction of serum fetuin A was associated with cardiovascular events (Spearman's rho -0.758, P<0.01). No significant difference was found between low and high serum fetuin A groups by Kaplan-Meier survival analysis (P=0.065).

CONCLUSIONReduced serum fetuin A may be a potential risk factor of coronary artery calcification, and can contribute to cardiovascular events in patients starting hemodialysis.

Adult ; Aged ; Blood Proteins ; metabolism ; Calcinosis ; blood ; etiology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Middle Aged ; Renal Dialysis ; adverse effects ; Risk Factors ; alpha-2-HS-Glycoprotein

OBJECTIVETo investigate potential pathophysiological role of cardiac mast cells accumulation and degranulation on the collagen deposition after coronary microembolization (CME).

METHODSCME was induced in miniswine by selective infusion of 15X10(4) microspheres (diameter, 45 mum) into the left anterior descending artery groups (CME group, n=8). Some CME-induced animals were pretreated with the MC stabilizer tranilast (50 mg/kg, twice daily), beginning 2 weeks before CME and thereafter throughout the experimental period (CME +tranilast group, n=8), while some animals received tranilast without CME (tranilast group, n=8). Eight sham-operated animals without CME served as controls. After 30 days, the total number of MC and degranulating MCs and collagen deposition was assessed by histological and electronic microscopy studies.

RESULTSThe numbers of total and degranulating MCs and collagen volume fraction (CVF) at day 30 in CME group were significantly higher than those in controls (P <0.01). Treatment with tranilast significantly reduced the numbers of total and degranulating MCs and CVF at day 30 (all P <0.01). There was a significant positive correlation of the CVF with the number of total MCs (r=0.91, P <0.001) and degranulating MCs (r=0.92, P <0.001) over the CME myocardium.

CONCLUSIONMCs accumulation and degranulating contribute to myocardial fibrosis collagen deposition.

Animals ; Cell Degranulation ; Collagen ; metabolism ; Coronary Vessels ; pathology ; physiopathology ; Embolism ; pathology ; physiopathology ; Mast Cells ; pathology ; physiology ; Myocardium ; metabolism ; pathology ; Swine ; Swine, Miniature