The Mechanism of Inflammatory Factors and Soluble Vascular Cell Adhesion Molecule-1 Regulated by Nuclear Transcription Factor NF-κB in Unstable Angina Pectoris.

This work is aimed at exploring the mechanism of inflammatory factors and soluble vascular cell adhesion molecule-1 (sVCAM-1) regulated by nuclear transcription factor-κB (NF-κB) in unstable angina pectoris (UAP). 60 patients with unstable angina pectoris (UAP), 60 patients with stable angina pectoris (SAP), and some healthy people (controls) were selected and included. Peripheral venous blood (PVB) of all subjects was collected to detect blood routine. The enzyme-linked immunosorbent assay (ELISA) was adopted for detecting Visfatin, sVCAM-1, soluble intervascular cell adhesion molecule-1 (sICAM-1), and inflammatory factors; flow cytometry (FCM) was to detect the CD63 and CD62P; real-time fluorescence quantitative polymerase chain reaction (rt-qPCR) was employed to detect the NF-κB1, NF-κB2, and REL mRNA. The hs-CRP results of UAP group, SAP group, and control group were 11.12 ± 1.5 mg/L, 10.23 ± 1.3 mg/L, and 4.51 ± 1.1 mg/L, respectively. The CD62P results of UAP group, SAP group, and control group were 16.07 ± 2.5%, 11.09 ± 1.8%, and 22.15 ± 0.4%, respectively. The high-sensitivity C-reactive protein (hs-CRP), inflammatory factors (IL-6, IL-17, IL-23, IL-1ß, and tumor necrosis factor α (TNF-α)), CD63, CD62P, NF-κB1, NF-κB2, and REL mRNA were obviously higher in the SAP group compared than the indicator values in the control group (P < 0.05). The relative REL expression results of UAP group, SAP group, and control group were 3.77 ± 1.5, 2.2 ± 0.6, and 1 ± 0.4, respectively. The inflammatory factors, Visfatin, sVCAM-1, sICAM-1, CD63, CD62P, NF-κB1, NF-κB2, and REL mRNA in the UAP group showed higher levels in contrast to the other two groups (P < 0.05). In summary, UAP patients had marked activation of the IL-23/IL-17 inflammatory axis, high expressions of sVCAM-1 and sICAM-1, and activation of the NF-κB pathway. Increase of inflammatory factors and sVCAM-1 regulated by NF-κB was closely correlated with UAP.

Involvement of enhanced expression of classical complement C1q in atherosclerosis progression and plaque instability: C1q as an indicator of clinical outcome.

Activation of the classical complement pathway plays a major role in regulating atherosclerosis progression, and it is believed to have both proatherogenic and atheroprotective effects. This study focused on C1q, the first protein in the classical pathway, and examined its potentialities of plaque progression and instability and its relationship with clinical outcomes. To assess the localization and quantity of C1q expression in various stages of atherosclerosis, immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) were performed using abdominal aortas from eight autopsy cases. C1q immunoreactivity in relation to plaque instability and clinical outcomes was also examined using directional coronary atherectomy (DCA) samples from 19 patients with acute coronary syndromes (ACS) and 18 patients with stable angina pectoris (SAP) and coronary aspirated specimens from 38 patients with acute myocardial infarction. C1q immunoreactivity was localized in the extracellular matrix, necrotic cores, macrophages and smooth muscle cells in atherosclerotic lesions. Western blotting and real-time PCR illustrated that C1q protein and mRNA expression was significantly higher in advanced lesions than in early lesions. Immunohistochemical analysis using DCA specimens revealed that C1q expression was significantly higher in ACS plaques than in SAP plaques. Finally, immunohistochemical analysis using thrombus aspiration specimens demonstrated that histopathological C1q in aspirated coronary materials could be an indicator of poor medical condition. Our results indicated that C1q is significantly involved in atherosclerosis progression and plaque instability, and it could be considered as one of the indicators of cardiovascular outcomes.

Characterization of the B cell receptor repertoire of patients with acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) is a complex cardiovascular disease whose development involves the dysregulation of adaptive immune responses. Though it has been proven that T cells associate with inflammation in the development of ACS, the function of B cells in disease remains unclear. OBJECTIVE: The aim of this study was to reveal the diversity of the B cell receptor (BCR) repertoire of patients with ACS. METHODS: We conducted a pilot study to sequence the immune repertoire of peripheral blood mononuclear cells (PBMCs) from patients with ACS, including acute myocardial infarction (AMI) and unstable angina (UA), and quantitatively characterized BCR repertoires by bioinformatics analysis. RESULTS: We found that patients with AMI and UA had lower BCR repertoire diversity compared with controls with normal coronary arteries (NCA). Lower percentages of productive unique BCR nt sequences and higher percentages of top 200 unique BCR sequences were identified in AMI and UA patients than NCA controls. Patients had various preferential usage of V and J genes from B cell clones in accordance with the disease severity of coronary arteries. AMI patients had distinct CDR3 amino acids, and their frequency differed among patients with ACS. CONCLUSIONS: Our results indicate that differential BCR signatures represent an imprint of distinct repertoires among ACS patients. This study thereby opens up the prospect of studying disease-relevant B cells to better understand and treat ACS.

Characterization of LncRNA expression profile and identification of functional LncRNAs associated with unstable angina.

BACKGROUND: Increasing evidences suggest that long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of coronary artery disease (CAD). However, the association between lncRNAs expression profiles and unstable angina (UA) remained poorly known. Thus, the present study aims to investigate expression patterns, biological functions, and diagnostic value of lncRNAs in UA. METHODS: The present study explored the lncRNA and mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of UA patients and normal coronary artery (NCA) controls using RNA-seq. The biological function of differentially expressed lncRNAs was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of the selected lncRNAs was validated in another 44 UA patients and 46 NCA controls. Receiver operating characteristic curve (ROC) was performed to evaluate the diagnostic value of lncRNAs for UA. RESULTS: A total of 98 lncRNAs and 615 mRNAs were observed differentially expressed in PBMCs of UA patients as compared to NCA controls. The 10 most upregulated lncRNAs were LNC_000226, DANCR, RP1-167A14.2, LNC_002091, LNC_001526, LNC_001165, LNC_002772, LNC_000088, LNC_001226, and FAM157C, and the 10 most downregulated lncRNAs were RP11-734I18.1, RP11-185E8.1, RP11-360I2.1, LNC_001302, LNC_001287, RN7SL471P, LNC_000914, LINC01506, RP11-160E2.6, and LNC_000995. LNC_000226 and MALAT1 have high area under the curve values (AUC) for distinguishing UA from NCA patients (0.810 and 0.799, respectively), and the combination of MALAT1 and LNC_000226 increased the AUC value to 0.878. CONCLUSIONS: The present study added our understanding about the lncRNA expression profile in UA patients and provided potential biomarkers for the diagnosis of UA.

The clinical role of combined serum C1q and hsCRP in predicting coronary artery disease.

OBJECTIVE: C1q has been shown to be associated with coronary heart disease (CAD) and can co-deposit with C-reactive protein (CRP) in atherosclerotic plaques. However, few studies have been conducted between C1q, CRP parameters and CAD. The aim of this study is to explore the relationship between C1q and CRP parameters and assess their clinical significance in CAD. METHODS: 238 total patients who underwent coronary artery angiography were enrolled and divided into control group (n = 65), stable CAD group (n = 47) and unstable angina group (UA group, n = 126). Patients' data were collected from self-administered questionnaires and electrical medical records. The severity of coronary stenosis was presented by Gensini score. The relationship between C1q, CRP parameters and CAD were evaluated by multivariate regression analysis and their predicting performance were assessed by ROC analysis and odds ratio analysis. RESULTS: Compared with control group, C1q was showed significantly lower in stable CAD (P = 0.004) and UA groups (P = 0.008), while hsCRP was higher in UA group (P = 0.024). Serum C1q was weakly positively associated with hsCRP (r = 0.24, P < 0.001) but not correlated with Gensini score. Logistic regression identified C1q (OR: 0.87 per 10 mg/L, 95% CI: 0.79-0.95, P = 0.001) and hsCRP (OR: 1.08 mg/L, 95% CI: 1.01-1.15, P = 0.032) as independent determinants of CAD. Furthermore, combined C1q and hsCRP level showed higher discriminatory accuracy in predicting CAD than C1q (AUC: 0.676 vs 0.585, P = 0.101; NRI: 10.4%, P = 0.049; IDI: 3.9%, P < 0.001) or hsCRP (AUC: 0.676 vs 0.585, P = 0.101; NRI: 16.7%, P = 0.006; IDI: 5.8%, P < 0.001). CONCLUSIONS: Reduced serum C1q and increased hsCRP are independently associated with CAD and could be potential predictors for CAD diagnosis. Furthermore, combined C1q and hsCRP showed better performance in predicting CAD than using single one.

Effects of hydrogen as adjuvant treatment for unstable angina.

Oxidative stress and inflammation are closely related to atherosclerotic cardiovascular disease. It is established that hydrogen has significant protective effects on many diseases as a potential antioxidative and anti-inflammatory agent. The purpose of this study is to evaluate the effect of hydrogen on unstable angina in vitro and in vivo. An atherosclerosis model in vitro was constructed by ox-LDL-induced injury of human umbilical vein endothelial cells and in vitro testing indicated hydrogen inhibited ox-LDL-induced oxidative stress and inflammatory response by down-regulating LOX-1/NF-kB signaling pathway. Subsequently, the attenuating effect of hydrogen-rich water intake on unstable angina was further confirmed in clinic. Forty hospitalized subjects with unstable angina were enrolled and consumed either 1000-1200 mL/d hydrogen-rich water or the same amount of placebo pure water in addition to conventional drugs for three months. Clinical analysis showed hydrogen-rich water intake relieved angina symptoms in unstable angina patients. Serum analysis showed that hydrogen-rich water addition resulted in more effective reductions of total-cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B levels compared with conventional treatment. These results support that hydrogen as adjuvant treatment has a beneficial effect on unstable angina.

Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain.

BACKGROUND: Despite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin. METHODS: The MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay. RESULTS: Lower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88-0.99). CONCLUSION: In patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.

Association Between Uric Acid and N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Unstable Angina Pectoris.

BACKGROUND: The association between uric acid and N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) in patients with unstable angina pectoris (UAP) is unclear. METHODS: We recruited 260 patients with UAP admitted to the first affiliated Hospital of Guangxi Medical University from February 2018 to August 2018. According to the level of uric acid, patients were divided into 4 groups (Q1 = 48.00-305.00 µmol/L; Q2 = 310.00-405.00 µmol/L; Q3 = 408.00-513.00 µmol/L; Q4 = 514.00-4330.00 µmol/L). The differences of NT-proBNP between groups and the relationship with cardiac function were compared. RESULTS: The average age of the 260 patients enrolled was 75.04 years. The NT-proBNP of the 4 groups showed an increasing trend, and there were significant differences between the 4 groups (<0.001). On the other hand, with the increase of cardiac function (New York Heart Association), the levels of NT-proBNP and uric acid also showed an upward trend (all P < 0.05). Pearson correlation analysis showed that there was a positive correlation between uric acid log10 transform and NT-proBNP log10 transform (r = 0.272, P < 0.001). After adjusting the potential confounding factors, elevated uric acid was still significantly related to the increase of NT-proBNP (Q2 versus [vs.] Q1: OR = 469.64, 95%CI -1396.77 to 2336.05; Q3 vs. Q1: OR = 1166.53, 95%CI -726.12 to 3059.18; Q4 vs. Q1: OR = 3204.78, 95%CI 1240.86-5168.70). In subgroup analysis, the relationship between uric acid and NT-proBNP was significant in males, but no difference was observed in females. CONCLUSIONS: In male patients with UAP, elevated uric acid is related to the increase of NT-proBNP, but this phenomenon is not obvious in female patients.

Coronary plaque redistribution after stent implantation is determined by lipid composition: A NIRS-IVUS analysis.

BACKGROUND: The composition of plaque impacts the results of stenting. The following study evaluated plaque redistribution related to stent implantation using combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) imaging. METHODS: The present study included 49 patients (mean age 66 ± 11 years, 75% males) presenting with non-ST elevation myocardial infarction (8%), unstable angina (49%) and stable coronary artery disease (43%). The following parameters were analyzed: mean plaque volume (MPV, mm3), plaque burden (PB, %), remodeling index (RI), and maximal lipid core burden index in a 4 mm segment (maxLCBI4mm). High-lipid burden lesions (HLB) were defined as by maxLCBI4mm > 265 with positive RI. Otherwise plaques were defined as low-lipid burden lesions (LLB). Measurements were done in the target lesion and in 4 mm edges of the stent before and after stent implantation. RESULTS: MPV and maxLCBI4mm decreased in both HLB (MPV 144.70 [80.47, 274.25] vs. 97.60 [56.82, 223.45]; maxLCBI4mm: 564.11 ± 166.82 vs. 258.11 ± 234.24, p = 0.004) and LLB (MPV: 124.50 [68.00, 186.20] vs. 101.10 [67.87, 165.95]; maxLCBI4mm: 339.07 ± 268.22 vs. 124.60 ± 160.96, p < 0.001), but MPV decrease was greater in HLB (28.00 [22.60, 57.10] vs. 13.50 [1.50, 28.84], p = 0.019). Only at the proximal stent edge of LLB, maxLCBI4mm decreased (34 [0, 207] vs. 0 [0, 45], p = 0.049) and plaque burden increased (45.48 [40.34, 51.55] vs. 51.75 [47.48, 55.76], p = 0.030). CONCLUSIONS: NIRS-IVUS defined HLB characterized more significant decreases in plaque volume by stenting. Plaque redistribution to the proximal edge of the implanted stent occurred only in LLB.

Comparison of prognostic significance between serum fibrinogen and Global Registry of Acute Coronary Events score for prognosis of patients with non-ST-elevation acute coronary syndromes undergoing percutaneous coronary intervention.

OBJECTIVE: An elevated fibrinogen level has been demonstrated to be a predictor of adverse coronary heart disease outcome. This study aimed to assess whether fibrinogen is a useful marker to predict the prognosis of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). Additionally, the prognostic accuracy of fibrinogen level was compared with that of the Global Registry of Acute Coronary Events (GRACE) score. METHODS: A total of 1211 patients with NSTE-ACS undergoing PCI were analyzed in a prospective cohort study. The enrolled patients were divided into a low fibrinogen group (n = 826, fibrinogen ≤ 3.49 mg/dl) and a high fibrinogen group (n = 385, fibrinogen > 3.49 mg/dl) based on a receiver operating characteristic (ROC) curve. The clinical endpoints were death and death/nonfatal reinfarction. An ROC curve analysis was performed and the area under the curve with a 95% confidence interval (CI) was derived and compared with those for the GRACE score to determine the diagnostic value of the serum fibrinogen level. RESULTS: Multivariate analysis showed that an elevated baseline fibrinogen level was an independent predictor of death/nonfatal reinfarction (hazard ratio = 1.498, 95% CI: 1.030-2.181, P = 0.035). The prognostic performance of fibrinogen was equivalent to that of the GRACE system in predicting clinical endpoints (C-statistic: z = 1.486, P = 0.14). CONCLUSION: Fibrinogen is an independent predictor of death/nonfatal reinfarction in patients with NSTE-ACS undergoing PCI, and its accuracy is similar to that of the GRACE system.

IL-37 Plays a Beneficial Role in Patients with Acute Coronary Syndrome.

BACKGROUND: Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated. METHODS: Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested. RESULTS: Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+ T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable. CONCLUSION: In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS.

Plasma levels of receptor interacting protein kinase-3 correlated with coronary artery disease.

BACKGROUND: Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity. METHODS: A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models. RESULTS: Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04-11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05). CONCLUSIONS: Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

Identification of potential plasma biomarkers and metabolic dysfunction for unstable angina pectoris and its complication based on global metabolomics.

Unstable angina pectoris (UA) is one of the most dangerous clinical symptoms of acute coronary syndrome due to the risk of myocardial ischemia, which can lead to high morbidity and mortality worldwide. Though there are many advantages in understanding the pathophysiology of UA, the identification of biomarkers for the diagnosis, prognosis, and treatment of UA remains a challenge in the clinic. A global metabolomics research based on ultra-performance liquid chromatography (UPLC) combined with Q-TOF/MS was performed to discover the metabolic profile of health controls, UA patients, and UA patients with diabetes mellitus (DM), and screen for potential biomarkers. Twenty-seven potential biomarkers were determined using pattern recognition. These biomarkers, which include free fatty acids, amino acids, lysoPE and lysoPC species, and organic acids, can benefit the clinical diagnosis of UA. Pathway analysis indicated that arginine and proline metabolism, glycerophospholipid metabolism, and purine metabolism were affected in the UA patients, uniquely. Additionally, alterations in the metabolic signatures between UA and UA-complicated DM were also explored. As a result, six differential metabolites with an area under the curve (AUC) of more than 0.85 were identified as biomarkers for the diagnosis of UA and UA complicated with DM. Pathway analysis implied tryptophan metabolism was a key metabolic pathway in UA patients with DM, which provides new insights into the pathological study and drug discovery of UA.

Targeted metabolomic analysis of plasma metabolites in patients with coronary heart disease in southern China.

Coronary heart disease (CHD), one of the leading causes of death in the world, is a complex metabolic disorder due to genetic and environmental interactions. The potential mechanisms and diagnostic biomarkers for different types of coronary heart disease remain unclear. Metabolomics is increasingly considered to be a promising technology with the potential to identify metabolomic features in an attempt to distinguish the different stages of CHD.We aimed to investigate serum metabolite profiling between CHD patients and normal coronary artery (NCA) subjects and identify metabolic biomarkers associated with CHD progression in an ethnic Hakka population in southern China.Using a novel targeted metabolomics approach, we explored the metabolic characteristics of CHD patients. Blood samples from 302 patients with CHD and 59 NCA subjects were collected that analyses using targeted liquid-chromatography coupled with tandem mass spectrometry (LC-MS).A total of 361 blood samples were determined using targeted LC-MS. Plasma concentrations for trimetlylamine oxide (TMAO), choline, creatinine, and carnitine were significantly higher in patients with CHD compared to the NCA cohort. Further, we observed that the concentration of the 4 metabolites were higher than that of the NCA group in any group of CHD, which including acute myocardial infarction (AMI), unstable angina (UA), and stable angina (SA). In addition, the diagnostic model was constructed based on the metabolites identified and the ROC curve of the NCA subjects and CHD patients were performed. For choline and creatinine, the AUCs ranged from 0.720 to 0.733. For TMAO and carnitine, the AUCs ranged from 0.568 to 0.600.In conclusion, the current study illustrates the distribution of 4 metabolites between CHD patients and NCA subjects. Metabolomics analysis may yield novel predictive biomarkers that will potentially provide value for clinical diagnosis of CHD.

Loss of Regulatory Immune Function in Coronary Artery Disease Patients from the Indian Population.

The pathogenic roles of inflammatory T cells and monocytes subsets have not been explored in different manifestations of coronary artery disease. We studied the frequency of these cells, their response to autoantigens, regulatory cell functional assay, foam cell formation and macrophage differentiation in 181 patients (stable angina, ST-elevated myocardial infarction (STEMI), NSTEMI, and unstable angina), and 34 controls and in samples collected during recurrent cardiac events and from patients showing clinical improvement. The proportion of Th17 cells and monocytes gradually increased in patients with stable angina at one end of the spectrum followed by NSTEMI, STEMI, and unstable angina at other end. Inflammatory cells were positively and inversely associated with recurrent events and clinical improvement, respectively. Patients showed expansion of Th17 cells in response to autoantigen (HSP60) and compromised Treg function. Our results suggest that stress-induced activation of inflammatory cells expands in the absence of regulatory control in CAD patients.

Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors.

BACKGROUND AND AIMS: Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). METHODS: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. RESULTS: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. CONCLUSIONS: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

Oxidative stress, antioxidants, and lipid profile in the serum and saliva of individuals with coronary heart disease: is there a link with periodontal health?

BACKGROUND: Oxidative stresses and dyslipidemia are an important risk factor in the development of coronary atherosclerotic complications like angina pectoris and myocardial infarction. The aim of this study was to find the relationship between the salivary lipid profile, lipid peroxidation and antioxidants and the periodontal health status of patients with acute coronary heart disease (CHD). METHODS: Forty patients who had experienced a recent attack of angina pectoris or myocardial infarction and another 40 noncardiac patients matched for age, sex and residence (control) were recruited. The lipid profile level, lipid peroxidation and antioxidant status were measured in the serum and saliva of all participants together with lactate dehydrogenase (LDH) and C-reactive protein. The studied parameters were then correlated with the periodontal status of the participant using the Clinical Periodontal Sum Score (CPSS). A multiple linear regression was used to assess the net effect of each set of independent variables on the outcome variable using SPSS-21. A P value ≤0.05 was considered statistically significant. RESULTS: Salivary total cholesterol, triglycerides, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, malondialdehyde, uric acid, superoxide dismutase and LDH levels increased with the upper tertile of the CPSS, while salivary high-density lipoprotein-cholesterol decreased with the upper tertile of the CPSS. CONCLUSIONS: Periodontal health status could be considered as an independent risk factor for acute CHD.

Atheroprotective effects of statins in patients with unstable angina by regulating the blood-borne microRNA network.

Experimental studies have demonstrated several effects of statins in acute coronary syndrome (ACS) that may extend their clinical benefit beyond the lipid profile modification itself. However, the precise underlying mechanism remains to be elucidated. microRNAs (miRNAs) serve significant roles in the pathophysiology of atherosclerotic plaque progression. The present study investigated the protective role of statins in patients with unstable angina (UA) by regulating the circulating miRNA network. miRNA array results demonstrated that there were 21 differentially expressed miRNAs in non­statin­treated patients with UA (n=8) compared with non­coronary artery disease controls (n=8), and 33 differentially expressed miRNAs in statin­treated patients with UA (n=8) compared with non­statin patients. TargetScan and miRanda programs were used to predict miRNAs target genes. miRNAs target genes in vascular endothelial cells and monocytes were clustered based on the CGAP SAGE library via the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform, and miRNA target genes in platelets were clustered based on a UP tissue­specific library via the DAVID platform. The PANTHER database via DAVID platform was used to perform signaling pathway analysis. The miRNA­gene/pathway network was visualized by Cytoscape software. Bioinformatic analysis suggested that statin­induced miRNAs functions were primarily enriched in angiogenesis, integrin and platelet derived growth factor signaling pathways in UA patients. In endothelial cells and platelets, statin­induced miRNAs primarily targeted the integrin signaling pathway, and in monocytes primarily targeted cytoskeletal regulation by the Rho GTPase signaling pathway. These results revealed that statins may serve systematic protective roles in UA patients by influencing the circulating miRNA regulatory network. Further studies are required to verify the functions of statin­induced miRNAs in endothelial cells, platelets and monocytes.

Association of Circulating IGFBP1 Level with the Severity of Coronary Artery Lesions in Patients with Unstable Angina.

Aims. Local IGFBP1 level was reported to affect the development of coronary artery plaque. This study investigated the association of circulating IGFBP1 level with the severity of coronary artery lesions in patients with unstable angina. Materials and Methods. In 112 consecutive patients with clinically diagnosed unstable angina, admitted from July 2014 to July 2015, we studied the correlations of circulating IGFBP1 and the severity of coronary artery disease (CAD). Results. All patients underwent scheduled coronary angiography, and 67 cases were diagnosed with critical and 45 with noncritical CAD. Of the 67 critical CAD patients, 41 (61.19%) presented with multivessel and 26 (38.81%) with single-vessel lesions. IGFBP1 levels were higher in patients with multivessel than those with single-vessel lesions. Moreover, the IGFBP1 level was positively correlated with the GRACE score. Among clinical variables, the IGFBP1 level was correlated with HDL-C. IGFBP1 alone (cutoff 20.86 ng/ml) demonstrated a sensitivity of 0.448 and specificity of 0.933 in predicting CAD. Combination of IGFBP1 and HDL-C had a sensitivity of 0.821 and specificity of 0.800 in predicting CAD. Conclusions. Circulating IGFBP1 level positively correlated with the severity of CAD. IGFBP1, when combined with HDL-C, might be useful in screening for high risk CAD patients.

Serum potassium levels, cardiac arrhythmias, and mortality following non-ST-elevation myocardial infarction or unstable angina: insights from MERLIN-TIMI 36.

BACKGROUND: In acute coronary syndrome (ACS), potassium levels <3.5 mEq/L are associated with ventricular arrhythmias. Current guidelines therefore recommend a potassium target >4.0 mEq/L in ACS. Our study evaluated the association between potassium levels, cardiac arrhythmias, and cardiovascular death in patients with non-ST-segment elevation myocardial infarction or unstable angina. METHODS: Potassium levels were measured in 6515 patients prior to randomization to receive either ranolazine or a placebo in the MERLIN-TIMI 36 trial. A seven-day continuous electrocardiographic assessment was obtained to determine the incidence of non-sustained ventricular tachycardia (NSVT) and ventricular pauses. The association between potassium levels and cardiovascular death was evaluated using a Cox proportional hazards regression model with multivariable adjustment. RESULTS: NSVT lasting for at least eight consecutive beats occurred more frequently at potassium levels <3.5 mEq/L than at potassium levels ⩾5 mEq/L (10.1 vs. 4.5%, p=0.03 for trend), whereas the inverse pattern was observed for ventricular pauses >3 s, which occurred more frequently at potassium levels ⩾5 mEq/L than at potassium levels <3.5 mEq/L (5.9 vs. 2.0%, p=0.03 for trend). There was a U-shaped relationship between the potassium level at admission and both early and late risk of cardiovascular death. Compared with patients with potassium levels of 3.5 to <4 mEq/L, a potassium level <3.5 mEq/L was associated with an increased risk of cardiovascular death at day 14 (2.4 vs. 0.8%, HRadj 3.1, p=0.02) and at one year (6.4 vs. 3.0%, HRadj 2.2, p=0.01). The risk of cardiovascular death at one year was also significantly increased at potassium levels ⩾4.5 mEq/L and a similar trend was noted at potassium levels ⩾5 mEq/L. CONCLUSIONS: The lowest risk of cardiovascular death was observed in patients with admission potassium levels between 3.5 and 4.5 mEq/L. Both lower and higher levels of potassium were associated with tachyarrhythmias and bradyarrhythmias, suggesting a potential mechanistic explanation for the increased risk of cardiovascular death at the extremes of potassium homeostasis.