Unstable Coronary Artery Disease Patients Research Articles

Elevated Levels of Circulating lncRNAs LIPCAR and MALAT1 Predict an Unfavorable Outcome in Acute Coronary Syndrome Patients.

Coronary artery disease (CAD) is a leading cause of mortality worldwide. In this study, we aimed to assess the potential of plasma long non-coding RNAs (lncRNAs) LIPCAR and MALAT1 and microRNAs (miRNAs) miR-142-3p and miR-155-5p to discriminate unstable CAD patients from stable ones. 23 stable angina (SA), 21 unstable angina (UA), and 50 ST-segment elevation myocardial infarction (STEMI) patients were enrolled; their plasma was collected. ncRNA plasma levels were evaluated using RT-qPCR. All measured ncRNA levels were significantly increased in UA patients' plasma compared to SA patients' plasma and in STEMI-with major adverse cardiovascular event (MACE) patients' plasma vs. STEMI-without MACE patients' plasma. ROC analysis showed that increased levels of LIPCAR and MALAT1 were associated with UA, and the prognostic model improved with the addition of miR-155-5p levels. The assessed lncRNAs discriminated between hyperglycemic (HG) and normoglycemic (NG) UA patients, and they were associated with MACE incidence in STEMI patients; this prediction was improved by the addition of miR-142-3p levels to the ROC multivariate model. We propose LIPCAR and MALAT1 as effective diagnostic markers for vulnerable CAD, their association with HG in UA patients, and as robust predictors for unfavorable evolution of STEMI patients.

Circulatory soluble LOX-1 is a novel predictor for coronary artery disease patients.

This study investigated the biomarker effect of soluble lectin-like oxidised low-density lipoprotein (sLOX-1) levels for the evaluation of stable and unstable coronary heart disease, correlating it with aging. This case-control study was conducted at the Cardiology Department of Xiangya Hospital between June 2015 and September 2018. Stable coronary artery disease (CAD) patients were confirmed by an invasive coronary angiogram, and American College of Cardiology as well as European Cardiology Society clinical protocols were used for the diagnosis of unstable CAD subjects. Plasma sLOX-1 levels were determined from 226 stable CAD patients, 138 unstable CAD subjects and 75 healthy participants by enzyme-linked immunosorbent assay. Plasma sLOX-1 expressions were significantly elevated in stable CAD patients (4.5-fold) and unstable CAD patients (5.8-fold) above that of volunteer healthy participants. Moreover, between the stable and unstable patient groups, sLOX-1 concentrations were also statistically significantly different (p < 0.001). Levels of plasma sLOX-1 in the healthy female (30-60 years), and stable and unstable CAD female subjects (61-84 years) were markedly elevated compared with healthy male (30-60 years), as well as stable and unstable CAD male patients (61-84 years) (p < 0.001). Besides, in the female unstable CAD (61-84 years) subjects, circulatory sLOX-1 expressions were much higher than in the younger female unstable CAD (30-60 years) patients (p < 0.001). The stable CAD patients were clearly differentiated from healthy subjects with a high sensitivity of the area under the curve (AUC = 0.895). Unstable CAD patients and healthy subjects were also markedly different with a high sensitivity, as shown by AUC (0.902). Stable and unstable CAD subjects were differentiated with an AUC of 0.867. Elevated plasma sLOX-1 levels could be regarded as a novel biomarker for detecting CAD patients and there was a significant association with gender and aging.

Release of MMP-2 in the circulation of patients with acute coronary syndromes undergoing percutaneous coronary intervention: Role of platelets

IntroductionMatrix metalloproteinases (MMPs) of atherosclerotic tissue contribute to plaque rupture triggering acute coronary syndromes (ACS). Several MMPs, including MMP-2, are also contained in platelets and released upon activation. An increase in circulating levels of MMP-2 has been reported in patients undergoing percutaneous coronary interventions (PCI), but its time-course and origin remain unclear. Aims of our study were to assess the time-course of MMP-2 release in blood of stable and unstable coronary artery disease patients undergoing PCI and to unravel the possible contribution of platelets to its release. MethodsPeripheral blood samples were drawn immediately before, 4 and 24 h after PCI from patients with ACS (NSTEMI or STEMI, n = 21) or with stable angina (SA, n = 21). Platelet-poor plasma and washed platelet lysates were prepared and stored for subsequent assay of MMP-2 and β-thromboglobulin (β-TG), a platelet-specific protein released upon activation. ResultsPlasma MMP-2 and β-TG increased significantly 4 h after PCI and returned to baseline at 24 h in ACS patients, while they did not change in SA patients. Platelet content of MMP-2 and β-TG decreased significantly 4 h after PCI in patients with ACS, compatible with intravascular platelet activation and release, while they did not change in patients with SA. ConclusionsPCI triggers the release of MMP-2 in the circulation of ACS patients but not in that of patients with SA. Platelets activated by PCI contribute to the increase of plasma MMP-2 releasing their MMP-2 content. Given that previous mechanicistic studies have shown that MMP-2 may sustain platelet activation and unstabilize downstream-located plaques and in the long term favour restenosis and atherosclerosis progression, these data may encourage the search for therapeutic agents blocking MMP-2 release or activity in ACS.

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression.

The aim of the study was to explore the clinical impact of circulatory miR-126 as a candidate for novel biomarker in patients with coronary artery disease (CAD) and its protective role against hypoxia/reoxygenation- (H/R-) exposed HUVEC cellular injury. A total of 278 subjects, which included 153 subjects with angiographically confirmed CAD, 70 unstable angina subjects, and 55 healthy individuals, along with 18-hour HR-induced HUVECs were recruited in this study. Plasma miR-126 levels were significantly downregulated in stable and unstable CAD patients as well as 18-hour HR-exposed HUVECs as compared with controls. Stable and unstable CAD subjects were significantly differentiated from healthy individuals with a predictive value of AUC 0.903 and 0.923, respectively. Moreover, peripheral circulatory miR-126 expressions in elderly (71-90 years) stable and unstable CAD patients were comparatively lower than younger (30-50 years) subjects. The caspase-3 activity, intracellular ROS concentrations, and cellular viabilities were evidently increased in 18-hour HR-exposed HUVECs than in normal cells (P < 0.001). On the contrary, mimic expressions of miR-126 prominently reduced caspase-3 activity and intracellular ROS levels and markedly enhanced HUVEC cellular viabilities (P < 0.001). LRP6 expressions were significantly elevated in HR-induced HUVECs, whereas overexpression of miR-126 remarkably decreased LRP6 expressions (P < 0.001). Plasma miR-126 could be used as a novel biomarker for early prediction of CAD subjects. Overexpression of miR-126 significantly improved HUVEC cellular viabilities by downregulation of LRP6 protein expression, suggesting a potential therapeutic target for CAD patients.

Association of the serum apelin, but not ghrelin, with the presence and severity of coronary artery disease

Increasing evidence suggests that apelin and ghrelin may participate in atherogenesis. We sought to investigate whether the serum levels of apelin and ghrelin are significantly different in patients with coronary artery disease (CAD) compared to patients with nonsignificant coronary stenosis and determine the correlation between these adipokines and the severity of coronary stenosis.The study population included 31 stable CAD patients, 38 unstable CAD patients, and 39 non-CAD subjects. Serum levels of apelin and ghrelin, fasting blood glucose, lipid parameters, hs-CRP and hematological indices were determined in all groups using routine standard laboratory procedures. Serum apelin levels were significantly lower in patient with unstable CAD (0.354 ± 0.063 ng/mL) compared to stable CAD patients (0.401 ± 0.045 ng/mL, p = 0.003) and non-CAD subjects (0.415 ± 0.055 ng/mL, p<0.001). In addition, serum apelin levels were inversely correlated with the severity of coronary stenosis in CAD patients (p<0.05). However, there was no significant difference in ghrelin levels among the 3 groups.This data may suggest that the presence of unstable CAD may be associated with lower serum apelin which may indicate the potential role of this peptide in the progression and destabilization of coronary plaques.

The clinical impact of serum sLOX-1 level in coronary artery disease patients as inferred from its implication in the in vitro protective effects of metoprolol against hypoxic injury of HUVECs

Abstract Background Ischemic coronary artery disease (CAD) is a major public health problem across the world. Early detection and appropriate management significantly reduced CAD-induced morbidities and death. Endothelial cells are pathogenically implicated. Purpose Our study was designed to investigate the role of the soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) in the in vitro protective effect of Metoprolol against hypoxia-induced injury of Human umbilical vein endothelial cells (HUVECs). Secondly, the clinical significance of variations in serum levels of sLOX-1 in patients with CAD was assessed. Methods In vitro, hypoxic injury model of HUVECs was established in an atmosphere of 1% O2, 95% N2, and 5% CO2 for 24 hours. The protective effect and mechanism of action of the cardio-selective beta-blocker Metoprolol at 10–6 μM concentration was investigated. Consented stable atherosclerotic CAD (n=150) and unstable angina pectoris patients (n=75) along with 150 healthy volunteer subjects were voluntarily enrolled in this ethically approved study. Invasive coronary angiogram with ≥50% stenosis at least in one major coronary artery was used for diagnosis. ESC/ACC/AHC/practical protocols were used for categorizing patients into stable or unstable CAD. Serum sLOX-1 level was measured using specific ELISA kit. The diagnostic significance of serum sLOX-1 levels was assessed by analyzing its area under the curve (AUC). Results In vitro hypoxic conditions induced high rate of cellular apoptosis, high levels of LOX-1 expression, reactive oxygen species (ROS) generation and LDH release from HUVECs after 24 hours incubation, compared to normoxic control cells. Metoprolol significantly decreased LOX-1 levels, and prevented the release of LDH and generation of ROS. This culminated into marked improvement in cellular viability of hypoxia-exposed HUVECs (p&amp;lt;0.001). Compared to healthy subjects, serum levels of sLOX-1s were significantly elevated in atherosclerotic stable and unstable CAD patients (p&amp;lt;0.001). Serum sLOX-1 levels were increased by 4.21 folds in stable CAD patients and by 6.373 folds in atherosclerotic unstable angina patients vs. healthy participants. Moreover, the levels in the two patients' groups were significantly different (p&amp;lt;0.001). In stable angina CAD patients, sLOX-1 AUC = 0.929; and in unstable CAD patients, AUC = 0.944, indicating that serum sLOX-1 levels clearly differentiated patients from healthy participants with high specificity and sensitivity. Conclusions Extrapolated from HUVECs hypoxia-induced injury model and the protective effect of Metoprolol, elevation of the circulating levels of sLOX-1 correlated with increased risks for atherosclerotic CAD and is a highly sensitive and specific biomarker for early detection of the disease. Funding Acknowledgement Type of funding source: None

MiR-423 is differentially expressed in patients with stable and unstable coronary artery disease: A pilot study.

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients’ risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.

Association of low serum level of secreted frizzled-related protein 5 (SFRP5) with the presence and severity of coronary artery disease

Introduction: Secreted frizzled-related protein 5 (SFRP5), an anti-inflammatory adipokine, is excreted by adipose tissue and may have protective effects on cardiovascular system. In the present study, the relationships of serum level of SFRP5 with the presence and severity of coronary artery disease (CAD) was investigated. Materials and methods: In the current study, 40 control subjects, 40 stable and 40 unstable CAD patients were included. Serum level of SFRP5 in all subjects in the study was determined by immunoassay method. The severity of CAD (based on Gensini score) was assigned by angiography examination. The status of conventional risk factors was also determined. Then, the association of SFRP5 with CAD severity and traditional CAD risk factors was explored. Results: Serum level of SFRP5 was lowest in unstable CAD, followed by stable CAD patients and then control subjects (P < 0.001). The correlation of SFRP5 with Gensini score was significant only in unstable CAD patients (P < 0.01). However, the correlation of SFRP5 with the traditional CAD risk factors was relatively significant and negative in all patients (P<0.05). SFRP5 had a reverse association with the presence of CAD. Conclusions: Decreased level of serum SFRP5 is associated with the presence and severity of CAD, highlighting its usefulness as a potential clinical biomarker.

Transcoronary gradients of HDL-associated MicroRNAs in unstable coronary artery disease

AimsMicroRNAs (miRNAs) are transported on high-density lipoproteins (HDLs) and HDL-associated miRNAs are involved in intercellular communication. We explored HDL-associated miRNAs concentration gradients across the coronary circulation in stable and unstable coronary artery disease patients and whether changes in the transcoronary gradient were associated with changes in HDL composition and size. MethodsAcute coronary syndrome (ACS, n=17) patients, those with stable coronary artery disease (stable CAD, n=19) and control subjects without CAD (n=6) were studied. HDLs were isolated from plasma obtained from the coronary sinus (CS), aortic root (arterial blood) and right atrium (venous blood). HDL-associated miRNAs (miR-16, miR-20a, miR-92a, miR-126, miR-222 and miR-223) were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. HDL composition was measured immunoturbidometrically or enzymatically. ResultsA concentration gradient across the coronary circulation was observed for all the HDL-associated miRNAs. In ACS patients, there was a significant inverse transcoronary gradient for HDL-associated miR-16, miR-92a and miR-223 (p<0.05) compared to patients with stable CAD. Changes in HDL-miRNA transcoronary gradients were not associated with changes in HDL composition or size. ConclusionHDLs are depleted of miR-16, miR-92a and miR-223 during the transcoronary passage in patients with ACS compared to patients with stable CAD.

A prospective cardiometabolism ApPRoach of mechanisms of coronary plaque rupture to apprehend patients at risk of recurrent events — The APPROACH registry

Despite improvement in management of coronary artery disease (CAD), recurrent coronary events remain frequent. The aim of this study is to assess predictive factors of plaque rupture, leading to an acute coronary syndrome (ACS) by combining metabolic evaluation and coronary plaque imaging. This study involved two cohorts of patients, one concerning stable CAD and one ACS patients. In both groups of patients, plaque imaging was performed with standard coronary angiogram and optimal coherence tomography (OCT) in the 3 main coronary vessels defined by diameter superior to 2.5 mm. Recurrent major adverse cardiac events were collected during follow-up. Comparison of stable and unstable CAD patients will be performed to try to characterize criteria of plaque vulnerability. The preliminary results regarding the ACS cohort are presented in this abstract. We included 48 patients with mean age of 60.5 years and 87.3% of men. A three-vessel atherosclerotic disease was found in 42% of patients. A total of 142 non-culprit coronary lesions were analysed by OCT for a mean run of 60.4 mm by artery and total of 5854 mm. B2/C complex lesions (AHA/ACC classification) were represented in 28.2% of patients. OCT analysis allowed to define coronary lesions with mean distance from ostium of 22.6 mm, mean stenosis length of 11.9 mm and mean minimum lumen area (MLA) of 3.95 mm 2 with 66.1% of patients with MLA < 4mm 2 . Lesions were distributed in 60% of fibro-fatty plaques, 34% of fibro-calcified plaques and 5% of neo-angiogenesis. Systematic plaque characterization on non-culprit lesions found 7 vulnerable thin-cap fibroatheroma plaques and 3 asymptomatic plaque ruptures. OCT analysis of non-culprit coronary lesions is feasible and allows to highlight vulnerable lesions such as asymptomatic plaque ruptures. Analysis of stable cohort, biomarkers and follow-up of patients are necessary to define predictive factors of plaque rupture.

Unwarranted variation of coronary stent choice in The Netherlands.

Unwarranted variation of coronary stent choice in The Netherlands.

Lipids, blood pressure and kidney update 2015.

The most important studies and guidelines in the topics of lipid, blood pressure and kidney published in 2015 were reviewed. In lipid research, the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial revalidated the concept “lower is better” for low density lipoprotein (LDL)-cholesterol as a target for therapy, increasing the necessity of treatment the high-risk patients to achieve LDL-C goals. After these results, ezetimibe might become the preferred additional drug in the combination therapy of lipid disorders because of oral dosage form and lower acquisition cost. However, for the statin-intolerant patients and those patients requiring essential reductions in LDL-C to achieve their goals, new therapies, including PCSK9 inhibitors remain promising drugs. In blood pressure research, American Heart Association (AHA)/American College of Cardiology (ACC) 2015 guidelines recommended a target for blood pressure below 140/90 mmHg in stable or unstable coronary artery disease patients and below 150/90 mmHg in patients older than 80 years of age, however the recent results of the Systolic Blood Pressure Intervention Trial (SPRINT) trial have suggested that there might be significant benefits, taking into account cardiovascular risk, for hypertensive patients over 50 without diabetes and blood pressure levels <120/80. In kidney research, reducing the progression of chronic kidney disease and related complications such as anemia, metabolic acidosis, bone and mineral diseases, acute kidney injury and cardiovascular disease is still a goal for clinicians.

The diagnostic value of circulating microRNAs for middle-aged (40–60-year-old) coronary artery disease patients

OBJECTIVE:Circulating microRNAs have been recognized as promising biomarkers for various diseases. The present study aimed to explore the potential roles of circulating miR-149, miR-424 and miR-765 as non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged (40–60-year-old) patients.METHODS:Sixty-five stable coronary artery disease patients (49–57 years old), 30 unstable coronary artery disease patients (49–58 years old), and 32 non-coronary artery disease patients (49–-57 years old) who were matched for age, sex, smoking habits, hypertension and diabetes were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. Circulating miRNA levels were measured by quantitative real-time polymerase chain reaction.RESULTS:Circulating miR-149 levels were decreased 4.49-fold in stable coronary artery disease patients (1.18 ± 0.84) and 5.09-fold in unstable coronary artery disease patients (1.04 ± 0.65) compared with non-coronary artery disease patients (5.30 ± 2.57) (p<0.001). Circulating miR-424 levels were reduced 3.6-fold in stable coronary artery disease patients (1.18 ± 0.60) and 5-fold in unstable coronary artery disease patients (0.86 ± 0.54) compared with non-coronary artery disease patients (4.35 ± 2.20) (p<0.001). In contrast, circulating miR-765 levels were elevated 3.98-fold in stable coronary artery disease patients (6.09 ± 2.27) and 5.33-fold in unstable coronary artery disease patients (8.17 ± 2.77) compared with non-coronary artery disease patients (1.53 ± 0.99) (p<0.001). Receiver operating characteristic curve analysis revealed that the respective areas under the curve for circulating miR-149, miR-424 and miR-765 were 0.938, 0.919 and 0.968 in stable CAD patients and 0.951, 0.960 and 0.977 in unstable coronary artery disease patients compared with non-coronary artery disease patients.CONCLUSION:Our results suggest that circulating miR-149, miR-424 and miR-765 might be novel, non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged patients. However, future prospective trials in large patient cohorts are necessary before reaching a solid conclusion.

Iron Status and Mortality in Stable and Unstable Coronary Artery Disease Patients

ObjectiveWe sought to assess the relationship of indices of iron status and the risk of all‐cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients with and without acute coronary syndrome (ACS).Methods and results: The study sample included 1181 CAD patients (692 with ACS and 489 with stable CAD). Cox proportional hazards regression models were used to estimate the association of circulating iron, ferritin and hepcidin with all‐cause and CVD mortality. After an average follow‐up of 4.1 years, 144 deaths were recorded, 108 of which were due to CVD. After adjusting for clinical CVD risk factors and inflammatory markers, ferritin and hepcidin were positively associated with CVD mortality in ACS group, hazard ratios (HR) (95% CIs) Q4 versus Q1: 4.05 (1.53‐10.7) and 2.86 (1.09‐7.48), respectively. Circulating iron showed an inverse association with CVD mortality in stable CAD group, HR (95% CI) Q4 versus Q1: 0.23 (0.08‐0.63). The discriminative abilities when including and excluding iron status into traditional clinical CVD models were 2.1% in all CAD patients, 3.1% in ACS patients, and 3.6% in stable CAD patients.ConclusionIron status was different in stable and unstable CAD patients. Circulating iron was inversely associated with the risks of mortality in stable CAD patients, while plasma ferritin and hepcidin were positively associated with mortality risks in ACS patients.

Circulating miR-765 and miR-149: potential noninvasive diagnostic biomarkers for geriatric coronary artery disease patients.

The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD) patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years) and 32 unstable CAD (72.03 ± 4.3 years) and 20 healthy subjects (71.7 ± 5.2 years), matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC) of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people.

Comparative Evaluation of Efficacy, Safety and Haemostatic Parameters of Enoxaparin and Fondaparinux in Unstable Coronary Artery Disease

To compare the safety and efficacy of Enoxaparin (EX) and Fondaparinux (FD) in patients with Unstable Coronary Artery Disease (UCAD). A prospective, open label, randomized comparative study was designed to study the comparative efficacy and safety of EX and FD in UCAD patients. Recovery, recurrence, major and minor bleeding and biochemical investigations were evaluated and compared among two arms. The baseline demographic characteristics were similar in both groups, with mean age of 56.05 and 56.05 years in EX and FD group respectively. Recovery was equal in two arms. Recurrent MI or angina was seen numerically more in EX group, but it did not statistically vary from that in the FD group. Incidence of haemorrhage was similar in both groups at 9 days, but at 30 days, EX showed a higher incidence (p<0.05). Deaths were prevented in both the treatment arms. Bleeding parameters such as BT, CT and platelet count were not altered in both groups. FD appeared to be better than EX in efficacy, as was indicated by a numerically more decrease in recurrence of angina or MI. FD regimen group also had better safety profile, as there was no incidence of haemorrhage at 30 days Therefore, we conclude that FD is an attractive option than EX in UCAD patients.

Elevated Plasma Myeloperoxidase Levels in Relation to Circulating Inflammatory Markers in Coronary Artery Disease

Elevation of the leukocyte enzyme myeloperoxidase (MPO) in stable coronary artery disease (CAD) is controversial and its relationship with oxidized low-density lipoprotein (ox-LDL) and nitrite/nitrate (NOx) levels in CAD patients has not been evaluated. Therefore, we sought to evaluate these relationships. This study included 50 stable CAD patients, 50 unstable CAD patients and 50 control subjects. Plasma MPO and ox-LDL levels were determined using enzyme immunoassay. Plasma NOx and other risk factors were also measured in the patients. Plasma MPO levels were higher in unstable CAD patients (71.2 ± 19.6 ng/ml) than in stable CAD patients (34.5 ± 6.8 ng/ml) and control subjects (23.0 ± 3.6 ng/ml) (p < 0.001). Furthermore, plasma MPO was positively correlated with ox-LDL and negatively correlated with NOx levels (p < 0.05). Plasma MPO levels were elevated in CAD patients and its relation to CAD may be through the oxidation of LDL and reduction of NO levels.

The peripheral blood mononuclear cell microRNA signature of coronary artery disease

Background MicroRNAs are being used in the oncology field to characterize tumors and predict the survival of cancer patients. Here, we explored the potential of microRNAs as biomarkers for coronary artery disease (CAD) and acute coronary syndromes. Methods and results Using real-time PCR-based profiling, we determined the microRNA signature of peripheral blood mononuclear cells (PBMCs) from stable and unstable CAD patients and unaffected controls. 129 of 157 microRNAs measured were expressed by PBMCs and low variability between separate PBMC pools was observed. The presence of CAD in general coincided with a marked 5-fold increase ( P < 0.001) in the relative expression level of miR-135a, while the expression of miR-147 was 4-fold decreased ( P < 0.05) in PBMCs from CAD patients as compared to controls, resulting in a 19-fold higher miR-135a/miR-147 ratio ( P < 0.001) in CAD. MicroRNA/target gene/biological function linkage analysis suggested that the change in PBMC microRNA signature in CAD patients is probably associated with a change in intracellular cadherin/Wnt signaling. Interestingly, unstable angina pectoris patients could be discriminated from stable patients based upon their relatively high expression level of a cluster of three microRNAs including miR-134, miR-198, and miR-370, suggesting that the microRNA signatures can be used to identify patients at risk for acute coronary syndromes. Conclusions The present study is the first to show that microRNA signatures can possibly be utilized to identify patients exhibiting atherosclerotic CAD in general and those at risk for acute coronary syndromes. Our findings highlight the importance of microRNAs signatures as novel tool to predict clinical disease outcomes.

Variants of the Interferon Regulatory Factor 5 Gene Regulate Expression of IRF5 mRNA in Atherosclerotic Tissue But Are Not Associated With Myocardial Infarction

Signaling events after activation of toll-like receptors (TLRs) are important mechanisms promoting inflammation in the atherosclerotic plaque. INF regulatory factor 5 (IRF5) is one of the mediators of downstream effects of TLRs. Several single nucleotide polymorphisms (SNPs) in the IRF5 gene have been found to be associated with systemic lupus erythematosus. We examined IRF5 mRNA expression in carotid atherosclerotic tissue (n=99) and the case-control association between SNPs in the IRF5 gene with myocardial infarction (MI) (n=376+387) and unstable coronary artery disease (CAD) (n=3101+445). Among unstable CAD patients, association of IRF5 SNPs with recurrent coronary events (n=401) was also investigated. The IRF5 mRNA expression was increased in atherosclerotic tissue compared with control tissue (P<0.001). Significant associations with IRF5 expression was observed for 6 of 10 SNPs in the study. However, the IRF5 SNPs examined were neither associated with the risk of precocious MI, nor with unstable CAD or risk of recurrent cardiovascular events in unstable CAD patients. IRF5 mRNA is expressed in cells in atherosclerotic tissue and its expression is modified by SNPs in the IRF5 gene. Genetic variation at the IRF5 locus was, however, not associated with CAD or related phenotypes.

Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease

Atherosclerosis is a chronic inflammatory disease and interleukins are considered to play a key role in the chronic vascular inflammatory response that is typical of atherosclerosis. The serum levels of several of these cytokines have been found to positively correlate with coronary arterial disease and its sequelae. The aim of our study was to evaluate the levels of a comparatively new cytokine IL-17, in patients with stable and unstable coronary artery disease in order to assess whether unstable coronary artery disease patients had higher IL-17 levels. We analyzed the concentrations of IL-17, IL-6, IL-8 and IL-10 using enzyme-linked immunosorbent assay and heat-sensitive C-reactive protein using latex particle-enhanced immunoturbidimetry in 58 consecutive unselected patients divided into three groups: stable angina (n=14), unstable angina (n=24) and acute myocardial infarction (n=20). We further compared them with 20 healthy controls. These 58 patients were also angiographically studied and divided into two groups: simple lesion (n=22) and complex lesion (n=36), on the basis of the coronary plaque morphology. Our results show increased concentrations of the proinflammatory cytokines IL-17, IL-6, IL-8 and heat-sensitive C-reactive protein, and decreased concentration of IL-10 in plasma of unstable angina and acute myocardial infarction patients. Plasma concentration of IL-17 was also positively correlated with plasma concentrations of IL-6 and heat-sensitive C-reactive protein. Our findings further showed that IL-17 values were higher in patients having angiographically visible complex types of lesions but no difference was observed between complex and simple lesion morphology patients. In conclusion, these findings point towards a role of inflammation in the form of increased activity of IL-17, IL-6 and IL-8 in patients of unstable angina and acute myocardial infarction and thus suggest that IL-17-driven inflammation may play a role in the promotion of clinical instability in patients with coronary artery disease.