Bioinformatics analysis reveals the potential role of matrix metalloproteinases in immunity and urolithiasis.

Background: The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall's plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation. Methods: The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA. Results: Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis. Conclusion: We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.

Relationship between Coronary Artery Tortuosity and Cardiorespiratory Fitness in Patients without Obstructed Coronaries.

OBJECTIVE: This study aimed to analyze the relationship between cardiorespiratory fitness (CRF) and the increasing severity of coronary artery tortuosity (CAT) in patients with non-stenosed coronaries. METHODS: A total of 396 patients who underwent coronary angiography and cardiopulmonary exercise testing (CPET) between August 2020 and July 2021 were included in this single-center retrospective study after excluding patients with significant coronary artery disease (≥50% stenosis). Patients were divided into two groups: no or mild coronary artery tortuosity (N/M-CAT) and moderate to severe coronary artery tortuosity (M/S-CAT) and laboratory electrocardiographic, echocardiographic, and CPET parameters were compared between two groups. RESULTS: M/S-CAT was found in 46.9% of the study participants, with 66.7% being women. M/S-CAT was significantly associated with advanced age (P=0.014) and females (P=0.001). Diastolic dysfunction parameters, E velocity (P=0.011), and E/A ratio (P=0.004) also revealed significant differences between the M/S-CAT group and N/M-CAT group. VO2@peak (1.22±0.39 vs. 1.07±0.39, P<0.01) and VO2@AT (0.77±0.22 vs. 0.71±0.21, P=0.017) were significantly lower in the M/S-CAT group than in the N/M-CAT group. Multivariate logistic regression analysis identified females (OR=0.448; 95% CI, 0.296-0.676; P=0.000) and E/A ratio (OR=0.307; 95% CI, 0.139-0.680; P=0.004) to be independent risk factors of M/S-CAT and showed no association of CPET parameters to M/S-CAT. CONCLUSION: The results indicate that increasing severity of CAT is strongly associated with female gender and E/A ratio and is not directly correlated with decreasing CRF. Further research with a larger patient population and a longer follow-up time is required to fully comprehend the impact of CAT on CRF.

Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography.

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<-21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (-13.7% ± 3.4% vs. -17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = -0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = -0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

Key Role of CD151-integrin Complex in Lung Cancer Metastasis and Mechanisms Involved.

Tetraspanin CD151 was found to be upregulated in malignant cell types and has been identified as a tumor metastasis promoter. In this study, we aimed to examine the role of the CD151-integrin complex in lung cancer metastasis and the underlying mechanisms. CD151 QRD194-196 →AAA194-196 mutant was generated and used to transfect A549 human lung adenocarcinoma cells. We found that there was no significant difference in CD151 protein expression between CD151 and CD151-AAA mutant groups. In vitro, CD151-AAA mutant delivery abrogated the migration and invasion of A549 cells, which was promoted by CD151 gene transfer. Furthermore, CD151-AAA delivery failed to activate FAK and p130Cas signaling pathways. Western blot and immunohistochemical staining showed strong CD151 expression in lung cancerous tissues but not in adjacent normal tissues. Increased level of CD151 protein was observed in 20 of the patients and the positive rate of CD151 protein in specimens was 62.5% (20/32). In addition, CD151 was co-localized with α3 integrin at the cell-cell contact site in carcinoma tissues. These results suggested that the disruption of the CD151-α3 integrin complex may impair the metastasis-promoting effects and signaling events induced by CD151 in lung cancer. Our findings identified a key role for CD151-α3 integrin complex as a promoter in the lung cancer.

Global Longitudinal Strain at Rest for Detection of Coronary Artery Disease in Patients without Diabetes Mellitus.

Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD). However, the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown. In the present study, 211 patients with suspected CAD were prospectively included, with DM patients excluded. All patients underwent echocardiography and subsequently coronary angiography within 3 days. Left ventricular (LV) GLSs were quantified by 2D STE. Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as an area stenosis ≥70% in ≥1 epicardial coronary artery (≥50% in left main coronary artery). Totally 145 patients were diagnosed as having critical CAD by coronary angiography. Significant differences were observed in all strain parameters between patients with and without critical CAD. The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of -19.05% with sensitivity of 78.1% and specificity of 72.7%, which increased to 0.926 after exclusion of apical segments (cut-off value -18.66%; sensitivity 84.4% and specificity 81.8%). The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries. The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery, left anterior descending (LAD) artery and right coronary artery (RCA), in order of diagnostic accuracy, was 0.818 for LCX, 0.764 for LAD and 0.723 for RCA, respectively. In conclusion, in non-DM patients with suspected CAD, GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy, and a higher cut-off point than reported before should be used. Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS. It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.

Treatment effects of systematic two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: rationale and design of a prospective, randomised and multicentre DEFINITION II trial.

INTRODUCTION: Provisional stenting (PS) for simple coronary bifurcation lesions is the mainstay of treatment. A systematic two-stent approach is widely used for complex bifurcation lesions (CBLs). However, a randomised comparison of PS and two-stent techniques for CBLs has never been studied. Accordingly, the present study is designed to elucidate the benefits of two-stent treatment over PS in patients with CBLs. METHODS AND ANALYSIS: This DEFINITION II study is a prospective, multinational, randomised, endpoint-driven trial to compare the benefits of the two-stent technique with PS for CBLs. A total of 660 patients with CBLs will be randomised in a 1:1 fashion to receive either PS or the two-stent technique. The primary endpoint is the rate of 12-month target lesion failure defined as the composite of cardiac death, target vessel myocardial infarction (MI) and clinically driven target lesion revascularisation. The major secondary endpoints include all causes of death, MI, target vessel revascularisation, in-stent restenosis, stroke and each individual component of the primary endpoints. The safety endpoint is the occurrence of definite or probable stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been approved by the Institutional Review Board of Nanjing First Hospital, and accepted by each participating centre. Written informed consent was obtained from all enrolled patients. Findings of the study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT02284750; Pre-results.

High-density lipoprotein cholesterol and in-hospital mortality in patients with acute aortic dissection.

The association between high-density lipoprotein cholesterol (HDL-C) and mortality in patients with acute aortic dissection (AAD) is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group (n=585), low HDL-C group (n=343) had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group (21.6% vs. 12.6%, log-rank=10.869, P=0.001). After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference (adjusted hazard ratio, 1.23; 95% confidence interval, 0.86-1.77; P=0.259). Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.

CYP2C8-derived epoxyeicosatrienoic acids decrease oxidative stress-induced endothelial apoptosis in development of atherosclerosis: Role of Nrf2 activation.

The aim of the present study is to investigate how cytochrome P450 enzymes (CYP) 2C8-derived epoxyeicosatrienoic acids (EETs) regulate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and protect against oxidative stress-induced endothelial injuries in the development and progression of atherosclerosis. In this study, cultured human umbilical vein endothelial cells (HUVECs) were transfected with CYP2C8 or pretreated with exogenous EETs (1 µmol/L) before TNF-α (20 ng/mL) stimulation. Apoptosis and intracellular ROS production were determined by flow cytometry. The expression levels of ROS-associated NAD(P)H subunits gp91 and p47, the anti-oxidative enzyme catalase (CAT), Nrf2, heme oxygenase-1 (HO-1) and endothelial nitric oxide synthase (eNOS) were detected by Western blotting. The results showed that CYP2C8-derived EETs decreased apoptosis of HUVECs treated with TNF-α. Pretreatment with 11, 12-EET also significantly blocked TNF-α-induced ROS production. In addition, 11, 12-EET decreased oxidative stress-induced apoptosis. Furthermore, the ability of 11, 12-EET to protect cells against TNF-α-induced apoptosis via oxidative stress was abrogated by transient transfection with Nrf2-specific small interfering RNA (siRNA). In conclusion, CYP2C8-derived EETs prevented TNF-α-induced HUVECs apoptosis via inhibition of oxidative stress associated with the Nrf2 signaling.

Analysis of clinical features of painless aortic dissection.

The clinical characteristics of painless aortic dissection were investigated in order to improve the awareness of diagnosis and treatment of atypical aortic dissection. The 482 cases of aortic dissection were divided into painless group and pain group, and the data of the two groups were retrospectively analyzed. The major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%) had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes, smoking and drinking history had no statistically significant differences between the two groups (P>0.05). The proportion of Stanford type A in painless group was significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The incidence of unconsciousness in the painless group was significantly higher than that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension in painless group was significantly higher than that in pain group for 4.26 folds (P=0.01). Computed tomography angiography (CTA) examination revealed that the incidence of aortic arch involved in the painless group was significantly higher than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that the incidence of painless aortic dissection was higher in Stanford A type patients, commonly seen in the patients complicated with hypotension and unconsciousness. CTA examination revealed higher incidence of aortic arch involvement.

[Bradykinin attenuates mechanical stress-induced myocardial hypertrophy through inhibiting the Ca²âº/ calcineurin pathway].

OBJECTIVE: To evaluate the inhibitory effect and related mechanism of bradykinin on mechanical stress induced myocardial hypertrophy. METHODS: Neonatal rat cardiomyocytes were isolated and cultured in silicon plates. All cardiomyocytes were randomly divided into three groups: control group, mechanical stretch group (mechanical stretch of silicon plates to 120% for 30 min) and mechanical stretch plus bradykinin group (1×10(-8) mol/L for 24 h before stretch). The protein synthesis and surface area of cardiomyocytes were detected by [(3)H] leucine incorporation and immunofluorescence of α-MHC, respectively. mRNA expression of atrial natriuretic peptide (ANP) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was detected by real time-PCR, the phosphorylation of calcineurin (CaN), the expression of Angiotensin II receptor 1 (AT1R) and angiotensin converting enzyme (ACE)by Western blot. RESULTS: The surface area of cardiomyocytes of mechanical stretch group [(973 ± 103) µm(2)] was significantly enlarged than in control group [(312 ± 29) µm(2)] and this effect could be partly attenuated by bradykinin [(603 ± 74) µm(2), all P < 0.05]. Mechanical stretch also significantly increased the protein synthesis, up-regulated the expression of ANP and decreased the expression of SERCA2, and these effects could be partly reversed by pretreatment with bradykinin. Moreover, bradykinin partly abolished the mechanical stretch-induced increases in CaN phosphorylation, up-regulation of AT1R but preserved the expression of ACE. CONCLUSIONS: Bradykinin significantly attenuates mechanical stretch-induced myocardial hypertrophy through inhibition of Ca(2+)/CaN pathway.

[Visfatin upregulates MMP-2 and MMP-9 expressions in human monocytes through activating NF-kappaB].

OBJECTIVE: To investigate the effects of visfatin on the MMP-2 and MMP-9 expressions in human monocytes and related mechanisms. METHODS: Human monocytes were isolated from blood, the expressions of MMP-2 and MMP-9 at mRNA and protein levels were detected in visfatin stimulated monocytes (0, 100, 200, 400 ng/ml) in the absence and presence of NF-kappaB inhibitor specific Bay11-7082 by Realtime PCR or Western blot, the MMP-2 and MMP-9 enzyme activity in the culture media was also detected by Gelatin Zymography. The NF-kappaB protein level and NF-kappaBp65 expression in visfatin stimulated cells were measured by Western blot and ELISA, respectively. RESULTS: Visfatin upregulated MMP-2 and MMP-9 expressions in human monocytes in a dose dependent manner. After treatment with visfatin 400 ng/ml for 24 h, comparing with the free visfatin treatment, the protein expressions of MMP-2 and MMP-9 were up-regulated to 1.644 +/- 0.052 and 3.578 +/- 0.081 (all P < 0.001); the enzyme activities of MMP-2 and MMP-9 were enhanced by 1.661 +/- 0.036 (P < 0.001) and 1.662 +/- 0.100 (P < 0.001). NF-kappaB was also activated in these cells by visfatin and these effects could be significantly attenuated by Bay11-7082. Visfatin induced a dose-dependent (100 - 400 ng) increase of NF-kappaBp65 nuclear translocation from 0.763 +/- 0.056 to 1.290 +/- 0.065 at 100 and 400 ng/ml, comparing with free visfatin treatment 0.467 +/- 0.046 (all P < 0.05). Bay11-7082 decreased the protein expression of MMP-2 and MMP-9 to 1.183 +/- 0.030 and 2.024 +/- 0.056 (all P < 0.001 comparing with 400 ng/ml visfatin treatment). CONCLUSION: Visfatin enhanced the expression and activity of MMP-2 and MMP-9 in human monocytes via activating NF-kappaB signaling pathway.

[Arteriogenesis induced by intramyocardial recombinant adeno-associated virus vector encoding human CD151 cDNA gene transfer in swines with coronary artery occlusion].

OBJECTIVE: To investigate the efficacy of CD151 gene delivery in promoting blood perfusion in swines after myocardial infarction. METHODS: Swines received coronary artery ligation and intramyocardial injection with rAAV-CD151, rAAV-anti-CD151 or rAAV-GFP. Eight weeks after vector injection, Western blot, immunostaining and 13N-labeled NH3 PET were performed to detect gene expression and biological effects of various treatments. RESULTS: High level of CD151 protein expression was detected in the rAAV-CD151 group. The capillary density in the rAAV-CD151 group [(83.8 +/- 6.7) n/mm2] was significantly higher than that in the control group [(33.2 +/- 4.5) n/mm2] and rAAV-GFP group [(41.6 +/- 5.6) n/mm2] (all P<0.05); the arteriole density in the rAAV-CD151 group [(16.4 +/- 2.5) n/mm2] was also higher than that in the control group [(6.6 +/- 2.3) n/mm2] and the rAAV-GFP group [(8.4 +/- 1.6) n/mm2] (all P<0.05). However, the lowest capillary density and arteriole density were evidenced in rAAV-anti-CD151 group. Myocardial blood perfusion was significantly increased in rAAV-CD151 group and significantly reduced in rAAV-anti-CD151 group (all P<0.05 vs. control). CONCLUSION: Intramyocardial injection of rAAV-CD151 could enhance the myocardial express of CD151 protein, increase capillary and arteriole densities and improve blood perfusion in swine with myocardial infarction.

Chronic inflammatory status in patients with coronary artery ectasia.

BACKGROUND: Coronary artery ectasia (CAE) is well-recognized, angiographic finding of abnormal coronary dilatation. The role of inflammation in atherosclerosis is increasingly well known. However, the association between inflammation and CAE has been controversial. METHOD: Fifty-five patients with CAE and non-obstructive coronary artery disease (CAD), 38 with obstructive CAD, and 33 angiographically normal coronary controls were enrolled in the study. The peripheral blood was taken, and white blood cell count (WBCC) as well as other leukocyte subtypes including neutrophils, lymphocytes, and monocyte cell count (MCC) were measured. The plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6) were determined by ELISA. RESULTS: The higher number of WBCC, neutrophil and MCC were found in patients with CAE compared with obstructive CAD patients as well as normal controls (p<0.01, respectively). Moreover, levels of plasma CRP and IL-6 were also significantly higher in patients with CAE than that in patients with obstructive CAD, and subjects without coronary artery disease (p<0.001, respectively). Univariate analysis showed that the sex, current smoking, numbers of WBCC, neutrophil, MCC, levels of CRP and IL-6 were related with CAE, while MCC was independently linked with a diagnosis of CAE. CRP was the independent variable most strongly associated with CAE by multivariate analysis. CONCLUSIONS: Taken together, this study confirmed and expanded previous limited findings that a more significant chronic inflammation might be linked with the pathogenesis of CAE that was associated with not only inflammatory markers but also inflammatory cells in patients with CAE.

Randomized comparison of early inflammatory response after sirolimus-eluting stent vs bare metal stent implantation in native coronary lesions.

BACKGROUND: The clinical significance of early inflammatory response after coronary stent implantation has been controversial. Sirolimus-eluting stent (SES) has been shown to be better outcomes compared with bare metal stent (BMS). We prospectively investigated the early inflammatory response after SES or BMS implantation in patients with single-vessel lesion, and evaluated the relationship between inflammation and late clinical outcomes in a randomized design. METHODS: Forty-eight patients with single-vessel disease were randomized into SES or BMS implantation group (n=24 respectively). Blood samples were taken before stenting, 1 h, 24 h and 8 months afterward. The plasma concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were determined by ELISA. The clinical and angiographic follow-up were performed at 8 months after stenting. RESULTS: There was no difference in baseline characteristics, plasma CRP and IL-6 concentrations between the 2 groups. However, plasma IL-6 concentrations at 1 h after stenting were higher in both groups than in baseline (p<0.01). In addition, the plasma CRP and IL-6 concentrations at 24 h after stenting were significantly higher in both groups compared with baseline (p<0.01 respectively). Likewise, plasma CRP and IL-6 concentrations were significantly higher in BMS group compared with SES group at 24 h after stenting (p<0.05 respectively). At the follow-up (mean 8 months after stenting), the rate of in-stent restenosis (ISR) and target lesion revascularization (TLR) were higher in BMS group than in SES group (p<0.05 respectively) although the plasma CRP and IL-6 concentrations are similar between the groups. CONCLUSIONS: Single coronary stenting could trigger an early inflammatory response. However, patients undergoing SES implantation has less augmentation of early inflammatory markers after stenting compared to patients treated with BMS, which was positively related the incidence of ISR and TLR at follow-up. This may reflect the potential impact of SES implantation on the early inflammatory response and late clinical outcomes.

Increased peripheral circulating inflammatory cells and plasma inflammatory markers in patients with variant angina.

BACKGROUND: Emerging data suggest that inflammation may play an important role in the pathogenesis of coronary artery disease. However, the relation of inflammatory status to coronary vasospasm has been less investigated in patients with variant angina (VA). PURPOSE: The aim of this study, therefore, was to determine peripheral circulating white blood cells as well as monocyte cells and plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels in patients with VA, and to compare patients with VA, stable coronary artery disease, and controls with angiographically normal coronary arteries. METHOD: Thirty-three consecutive patients with documented VA, 26 with stable coronary artery disease, and 22 normal controls (with angiographically normal coronary arteries) were involved in this study. The peripheral blood was taken, and white blood cells and monocyte cells were counted. The plasma concentrations of CRP and IL-6 were also evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The data showed that white blood cell counts and monocyte cell counts were significantly higher in patients of the VA group than in the other two groups (white blood cell counts: 7340+/-1893/mm vs. 6187+/-1748/mm vs. 5244+/-1532/mm, P<0.05, respectively; monocyte cell counts: 510+/-213/mm vs. 425+/-209/mm vs. 383+/-192/mm, P<0.05, respectively). Similarly, levels of plasma CRP and IL-6 were also significantly higher in patients of the VA group than in patients with stable coronary artery disease (CRP: 0.42+/-0.21 mg/l vs. 0.27+/-0.14 mg/l; IL-6: 10.4+/-1.0 pg/dl vs. 6.2+/-0.7 pg/dl, P<0.01, respectively), and patients with normal controls (CRP: 0.42+/-0.21 mg/l vs. 0.17+/-0.10 mg/l; IL-6: 10.4+/-1.0 pd/dl vs. 3.0+/-0.7 pg/dl, P<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with VA. CONCLUSION: Taken together, these findings suggested that more chronic, severe inflammation might be involved in the pathogenesis of VA, manifested by increased counts of circulating inflammatory cells and elevated plasma levels of CRP and IL-6.

Potential role of adipocytokine leptin in acute coronary syndrome.

By activating immune cells or a direct action on the vascular wall, leptin may affect the initiation and progression of atherosclerosis. We investigated whether plasma leptin concentration is associated with coronary artery disease, with particular focus on the relationship between plasma leptin and the development of an acute coronary syndrome. Plasma leptin, interleukin-6 and high-sensitivity C-reactive protein were measured in 34 patients with acute coronary syndrome and 21 with stable angina. Their results were compared with those of 21 normal controls. Plasma leptin levels were significantly higher in the acute coronary syndrome group (13.36 +/- 5.02 ng.mL(-1)) compared to the stable angina group (8.97 +/- 4.06 ng.mL(-1)) or normal controls (5.14 +/- 2.75 ng.mL(-1)). Interleukin-6 and high-sensitivity C-reactive protein were also higher in the acute coronary syndrome group, and leptin correlated positively with interleukin-6 and high-sensitivity C-reactive protein. These findings suggest that plasma leptin levels may be a useful marker of systemic inflammation, and measurement of plasma leptin may be helpful in assessing the risk of developing coronary heart disease.

Elevated circulating inflammatory markers in female patients with cardiac syndrome X.

BACKGROUND: The pathophysiological mechanism in cardiac syndrome X has been suggested as impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. However, despite the extensive studies, the precise mechanisms in cardiac syndrome X remain unclear. PURPOSE: The present study was, therefore, to investigate whether inflammatory cells and markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) might be involved in the pathogenesis of cardiac syndrome X. METHODS: Thirty-six female patients with cardiac syndrome X and 30 sex-matched normal controls were prospectively enrolled in this study. Blood samples were drawn for measuring white blood and monocyte cells, inflammatory markers such as CRP and IL-6, and data were compared between patients with cardiac syndrome X and normal controls. RESULTS: The data showed that increased numbers of white blood and monocyte cells were found in patients with cardiac syndrome X compared with normal controls (white blood cells: 7072+/-1146/mm(3) vs. 6138+/-1079/mm(3); monocyte cells: 612+/-186/mm(3) vs. 539+/-190/mm(3)p<0.05, respectively). Moreover, patients with cardiac syndrome X were detected to have significantly higher plasma CRP and IL-6 levels in comparison with patients with normal controls (CRP: 0.48+/-0.26 mg/L vs. 0.22+/-0.15 mg/L; IL-6: 13.4+/-1.2 pg/dl vs. 6.2+/-0.6 pg/dl, p<0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with cardiac syndrome X. CONCLUSIONS: Our data suggested that low-grade, chronic inflammation might contribute to the development of cardiac syndrome X manifested by increased plasma levels of inflammatory cells and inflammatory markers.