Feasibility of Distal Radial Access for Coronary Angiography and Percutaneous Coronary Intervention: A Single Center Experience.

OBJECTIVE: Asymptomatic radial artery occlusion remains the most common complication in transradial coronary interventional procedure. To prevent radial artery occlusion, distal transradial access (dTRA) has been suggested recently. In this article, we aim to describe our experience and to assess feasibility and safety of this new access site for routine coronary angiography (CAG) and percutaneous coronary intervention (PCI). METHODS: We retrospective analyzed 1,063 consecutive patients who were assigned to undergo CAG or procedural PCI through dTRA between 1 January 2018 and 31 December 2019 at Affiliated Zhongshan Hospital of Dalian University. The size of radial sheath used was 5 or 6 French. The sheath was removed at procedure termination, and hemostasis was obtained by compression bandage with gauze. The success rate of dTRA access defined by successful radial artery cannulation on the first dTRA side attempted, the cause of access failure, the hemostasis duration, the incidence of post-catheterization radial artery occlusion, and the other access-related complications including hematoma of forearm and thumb numbness were assessed. RESULTS: Radial artery cannulation via dTRA was successful in 953 of 1,063 patients with a success rate of 89.7%. Mean age of successful cases was 64.6 ± 11.2 years (26-94 years) with 339 (35.6%) women. A total of 363 (38.1%) cases were PCI. Among them, 95 cases (10%) underwent urgent PCI, including primary PCI in 64 patients with ST-segment elevation myocardial infarction and immediate PCI (<2 h from hospital admission) in 31 patients with very high-risk non-ST-segment elevation acute coronary syndrome. A total of 269 (28.2%) cases were via left dTRA. The 6 French sheath was used in 602 (63.2%) cases. Hemostasis was obtained within 2 h in 853 (89.5%) patients. There were 110 (10.3%) procedural failures: 59 (5.6%) cases of artery puncture failure, 49 (4.9%) cases of guide wire insertion failure, and 2 (0.2%) cases of sheath insertion failure. Complications potentially related to distal radial access included radial artery occlusion at the access site (13 cases, 1.4%), forearm radial artery occlusion (4 cases, 0.4%), hematoma of forearm (5 cases, 0.5%), and transient thumb numbness (2 cases, 0.2%). CONCLUSION: dTRA is a feasible and safe access and can be used as a rational alternative to traditional radial access for routine coronary interventional procedure.

Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice.

Histone modifications play an important role in the occurrence and development of atherosclerosis in human and atherosclerosis-prone mice. Histone methylation in macrophages, monocytes and endothelial cells markedly influence the progression of atherosclerosis. However, it remains unclear whether treatment with a histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibitor may suppress atherosclerosis. The present study aimed to determine the effects of the EZH2 inhibitor, GSK126, on the suppression and regression of atherosclerosis in apolipoprotein E-deficient mouse models. In vitro, it was found that pharmacological inhibition of EZH2 by GSK126 markedly reduced lipid transportation and monocyte adhesion during atherogenesis, predominantly through increasing the expression levels of ATP-binding cassette transporter A1 and suppressing vascular cell adhesion molecule 1 in human THP-1 cells. In vivo, it was found that atherosclerotic plaques in GSK126-treated mice were significantly decreased when comparing with the vehicle-treated animals. These results indicated that the GSK126 has the ability to attenuate the progression of atherosclerosis by reducing macrophage foam cell formation and monocyte adhesion in cell and mouse models. In conclusion, the present study provided new insights into the molecular mechanism behind the action of GSK126 and suggested its therapeutic potential for the treatment of atherosclerosis.

Atorvastatin suppresses vascular hypersensitivity and remodeling induced by transient adventitial administration of lipopolysaccharide in rats.

BACKGROUND: The phenotypic transition of vascular smooth muscle cells (VSMCs) from a contractile to a proliferative state markedly affects the pathophysiology of cardiovascular diseases. The adventitial inflammation can promote neointimal formation and vascular remodeling. We used direct administration of lipopolysaccharide (LPS) into the periphery of the carotid artery to investigate the influence of transient adventitial inflammation on vascular remodeling and its potential mechanism. METHODS: Male 15-week-old Wistar rats were randomly assigned to four groups with six rats in each group. The rats of groups I and II were administered distilled water, and group III and IV were treated with fasudil and atorvastatin respectively. All treatments were given daily for 11 days. On day 8, the adventitia in group I was injected with 5 µL sterile saline, and the group II-IV were injected with 5 µL sterilized LPS. The carotid blood flow and femoral blood pressure were measured in vivo, and the thickness of vascular intima and middle layer was measured in vitro. Serum interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) were determined using enzyme-linked immunosorbent assay (ELISA) assay. And the Rho-associated coiled-coil-containing protein kinase 2 (ROCK2), myosin phosphatase target subunit 1 (MYPT1), myosin light chain (MLC), myocardin, SM-α actin or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were detected by western blot. The comparisons were made by one-way analysis of variance with Bonferroni's post hoc test. A value of P<0.05 was considered to represent a statistically significant difference. RESULTS: Transient adventitial inflammation induced by LPS caused no obvious change in basal blood flow, but did lead to vascular hypersensitivity to serotonin. Morphological examinations revealed that the medial layer was the only domain affected, and showed VSMC proliferation and rearrangement. LPS increased serum IL-6 and TNFα contents, ROCK2 expression and activity, and caused changes in the expression levels of some stereotypical VSMC genes. Similar to the Rho-kinase inhibitor fasudil, atorvastatin completely restored the morphological alterations, even increased blood flow. CONCLUSIONS: Our study confirms the beneficial effect of atorvastatin on the vascular system in terms of morphology and function.

Beneficial effects of early administration of recombinant human B-type natriuretic peptide in ST-elevation myocardial infarction patients receiving percutaneous coronary intervention treatment.

INTRODUCTION: We aimed to evaluate the clinical performance of early administration of recombinant human B-type natriuretic peptide (rhBNP) to ST-elevation myocardial infarction (STEMI) patients receiving percutaneous coronary intervention (PCI) treatment. METHODS: In total, 185 patients diagnosed with STEMI were enrolled and randomised into either the placebo-treated (n = 88) or rhBNP-treated (n = 97) group. Patients were given either saline or rhBNP ten minutes before PCI and monitored with various cardiac parameters, including accelerated idioventricular rhythm, frequent ventricular premature beat (FVPB), ventricular tachycardia, systolic blood pressure, thrombolysis in myocardial infarction (TIMI) 3 gradation, corrected TIMI frame count (cTFC) and myocardial blush grade (MBG) 3 classification. RESULTS: Our results revealed no difference in accelerated idioventricular rhythm between the two groups. However, FVPB and ventricular tachycardia were significantly decreased in rhBNP-treated patients compared to placebo-treated patients (p < 0.05). Moreover, the occurrence ratio of reperfusion-associated low blood pressure in rhBNP-treated patients was lower than in placebo-treated patients (p = 0.03), while no difference was observed in infarction-related arteries TIMI 3 blood flow between the two groups (p = 0.23). Importantly, measurement of post-reperfusion blood flow velocity via cTFC suggested that rhBNP treatment could significantly increase blood circulation (p = 0.003). After stent implantation, the acquisition rate of MBG 3 was higher in rhBNP-treated patients compared to placebo-treated patients (p = 0.071), although the difference was not significant. CONCLUSION: We concluded that early administration of rhBNP can ameliorate the severity of reperfusion injury for STEMI patients receiving PCI treatment.

Plasma miR-18 Screens Acute Myocardial Infarction from Healthy Controls by Targeting Hypoxia Inducible Factor 1α.

BACKGROUND: This study aims to evaluate the expression of plasma miR-18, thereby evaluating its potential use as a biomarker to screen acute myocardial infarction (AMI) patients from healthy controls. METHODS: Real time PCR was carried out to evaluate the level of miR-18 in AMI patients and healthy controls. ROC analysis was performed to evaluate whether miR-18 could be used as a potential biomarker. Dual luciferase assay was used to identify the potential target of miR-18. RESULTS: We showed novel data that plasma miR-18 was significantly greater in AMI patients than in healthy controls. ROC analysis indicated that plasma miR-18 could screen AMI patients from healthy controls with high sensitivity and specificity. Further study demonstrated that plasma miR-18 was positively correlated with serum cardiac troponin I (cTnI) and creatine phosphokinase-MB (CK-MB) concentrations. Additionally, plasma miR-18 was increased in AMI patients with more stenosed coronary vessels. More importantly, plasma miR-18 was decreased in AMI patients after receiving percutaneous coronary intervention (PCI). Dual luciferase reporter assay indicated that overexpression of miR-18 significantly suppressed the relative luciferase activity of pmirGLO- HIF1α-3´UTR. CONCLUSIONS: In summary, enhanced plasma miR-18 could be used as a potential biomarker to screen AMI patients from healthy controls via targeting HIF1α.

Decreased miR-208 induced ischemia myocardial and reperfusion injury by targeting p21.

Aberrant expression of miR-208 was previously reported in cardiomyocytes after cardiac ischemia reperfusion (CIR) injury. However, the underlying mechanism has never been elucidated. In the current study, the relative level of miR-208 was determined in the hearts of CIR injury mice models using real time PCR. The effect of miR-208 on cardiomyocytes apoptosis was determined by Hoechst staining and annexin V-PI staining. Meanwhile, caspase3 activity was explored using an assay kit. To identify left ventricular fraction and relative wall thickness, the two-dimensional echocardiography was applied. Dual luciferase assay was applied to determine the target gene of miR-208. Compared with normal control, the level of miR-208 was significantly reduced in the hearts of CIR injury mouse models. Further studies revealed that reduction of miR-208 contributed to reactive oxygen species (ROS) production in the cardiomyocytes. We also found that inhibition of miR-208 prompted cardiomyocyte apoptosis. More importantly, the phosphorylation level of Akt and p38 was enhanced in primary cardiomyocytes transfected with miR-208 inhibitor, indicating a potential stress-response after CIR injury in primary cardiomyocytes. Dual luciferase assay and western blot analysis showed that transfection with miR-208 markedly suppressed the protein expression of p21, suggesting p21 was a target gene of miR-208. To conclude, we showed that reduced miR-208 level enhanced cardiomyocyte apoptosis mainly by targeting p21.

[Effect of valsartan on vasoconstriction induced by the chronic injury of the adventitia in the rat collared carotid artery].

OBJECTIVE: Vasoconstriction and vascular hypersensitivity to serotonin were previously shown in animal models of adventitia injury. We investigated the contribution of angiotensin II (AngII)/AngII receptors and oxidative stress to vascular contractility and reactivity in this model. METHODS: Wistar Kyoto rats were divided into 3 groups: normal (n = 6, no any intervention, only for measuring the serum AngII concentration), vehicle (n = 12, collared), and valsartan (n = 12, collared + valsartan 30 mg×kg(-1)×d(-1)). After one week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for one week. Blood flow and vascular reactivity to serotonin were determined one week after injury, the blood from left ventricle was taken to measure the serum AngII concentration by ELISA, and carotids were harvested for morphometry and Western blot analysis. RESULTS: Adventitia injury induced lumen cross-sectional area reduction (-44% vs. -5%), media diameter increase (62% vs. 10%), blood flow reduction [(2.79 ± 0.22) vs. (4.33 ± 0.84) ml/min] were significantly attenuated by valsartan. The increased vascular reactivity sensitivity to serotonin in vehicle group was also significantly reduced in valsartan group. Serum AngII concentration was significantly increased in vehicle group [(45.21 ± 4.52) pg/ml vs. (19.83 ± 0.5) pg/ml in normal rats, P = 0.0148] and the expression of AngII type 1 (AT(1)) receptor, AngII type 2 (AT(2)) receptor, as well as p22(phox) in collared arteries were significantly upregulated. Valsartan did not affect the AT(1) receptor expression but further increased serum AngII concentration [(89.73 ± 20.44) pg/ml vs. (45.21 ± 4.52) pg/ml, P = 0.001], and AT(2) receptor expression, while downregulated p22(phox) expressions. CONCLUSIONS: Collar-induced adventitia injury resulted in chronic vasoconstriction and vascular hypersensitivity to serotonin via increased serum AngII level, upregulated AngII receptors expression in the vascular well, and activated local oxidative stress. These changes could be blocked by valsartan suggesting a crucial role of AngII/AngII receptors on vascular contractility and reactivity changes in this model.

Involvement of Rho-kinase in collar-induced vasoconstriction and vascular hypersensitivity to serotonin in rat carotid.

BACKGROUND: Vasoconstriction and vascular hypersensitivity to serotonin has been described previously in animal models of adventitia injury. The present study was undertaken to investigate the contribution of the RhoA/Rho-kinase pathway to the collar-induced the change of vascular contractility and reactivity in rat carotid artery. METHODS: Wistar Kyoto rats were assigned to 4 treatments (n=12): vehicle, fasudil, valsartan, and fasudil plus valsartan. After 1 week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for 1 week. Blood flow and vascular reactivity to serotonin was determined 1 week after injury, and carotids were harvested for morphometry and biochemical analysis. RESULTS: Adventitia injury leaded to histological changes of vasoconstriction with the percent lumen patency of 54.5 ± 4.3% (p<0.001) decreasing, accompanying by the reduction of the blood flow (2.79 ± 0.22 ml/min vs. 3.67 ± 0.26 mi/min/p<0.001) when compared to contralateral arteries. The increase of vascular reactivity sensitivity to serotonin was observed in the collared artery when compared with the contralateral artery. Treatment with valsartan and fasudil prevented the development of vasoconstriction, improved the carotid blood flow and normalized the hypersensitivity to serotonin. Injury increased Angiotensin II type 1(AT(1)receptor, Rho-kinase, and p-MYPT1(Thr696) expression. Valsartan lowered the Rho-kinase and p-MYPT1(Thr696) expression. Fasudil inhibited the p-MYPT1(Thr696) expression. CONCLUSIONS: Collar-induced adventitia injury resulted in the enhancement of vascular contractility and reactivity. The activation of RhoA/Rho-kinase signal pathway, stimulated by AT(1) receptor, plays an important role in the collar-induced the change of vascular contractility and reactivity.