The effects of YKL-40 on angiogenic potential of HUVECs are partly mediated by syndecan-4.

Background: YKL-40, a secreted glycoprotein, has a role in promoting tumor angiogenesis through syndecan-1 receptor. Syndecan-4 is a member of syndecan family. However, the effects of YKL-40 on migration and tube formation of human umbilical vein cells (HUVECs) mediated by syndecan-4 receptor are unknown. Materials and methods: HUVECs were transfected with lentivirus encoding syndecan-4 short hairpin (sh) RNAs (lenti-synd4 shRNAs) and the efficiency of transfection was measured using qRT-PCR and western blotting. The effects of recombinant protein of YKL-40 on migration and angiogenesis of HUVECs adjusted by syndecan-4 were determined by wound healing and tube formation assay. The expressions of protein kinase Cα (PKCα) and extracellular signal regulated kinases (ERKs) 1 and 2 (ERK1/2) in HUVECs were measured using western blotting. Results: The mRNA and protein expression of syndecan-4 were significantly decreased in HUVECs successfully transfected with lenti-synd4 shRNAs. Lenti-synd4 shRNAs remarkably inhibited the migration and tube formation of HUVECs stimulated by recombinant protein of YKL-40. The levels of PKCα and ratio of p-ERK1/2 to ERK1/2 in HUVECs were also decreased by down-regulating syndecan-4. Conclusion: The effects of YKL-40 on migration and tube formation of HUVECs are partly inhibited by knock-downing syndecan-4 through suppressing PKCα and ERK1/2 signaling pathways.

Downregulation of Interleukin-13 Receptor α2 Inhibits Angiogenic Formation Mediated by Chitinase 3-Like 1 in Late Atherosclerotic Lesions of apoE-/- Mice.

Aim: Chitinase 3-like 1 (CHI3L1) has the potential to prompt proliferation and angiogenic formation. Interleukin-13 receptor α2 (IL-13Rα2) was regarded as a receptor of CHI3L1; however, it is unknown whether CHI3L1 adjusts the neovascularization in late atherosclerotic lesions of apoE -/- mice via IL-13Rα2. Methods: Silicone collars were placed around one of the common carotid arteries of apoE -/- mice fed with a high-fat diet. The mice were further injected with Ad.CHI3L1 alone or Ad.CHI3L1 + Ad.IL-13Rα2 shRNA through the caudal vein. The plaque areas in the whole aorta and aortic root were evaluated by Oil Red O staining and H&E staining. The contents of CD31, CD42b, and collagen in carotid plaques were investigated by immunohistochemistry and Masson trichrome staining. The role of CHI3L1 in migration and tube formation of human umbilical vein endothelial cells (HUVECs) was determined by transwell and Matrigel tests. The effect of CHI3L1 on the expression of AKT and extracellular signal-regulated kinase (ERK) was evaluated with the Western blot. Results: The plaque loads in the aorta were significantly more extensive in apoE -/- mice injected with Ad.CHI3L1 than those with Ad.CHI3L1 + Ad.IL-13Rα2 shRNA. CHI3L1 significantly increased the contents of CD31 and CD42b and decreased the element of collagen in late-stage atherosclerotic lesions of the carotid arteries. The effects of CHI3L1 on migration, tube formation, and upregulation of phospho-AKT and phospho-ERK of HUVECs were prohibited by inhibitors of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) as well as IL-13Rα2 shRNA. Conclusion: To some extent, CHI3L1 promotes migration and tube formation of HUVECs and neovascularization in atherosclerotic plaques possibly mediated by IL-13Rα2 through AKT and ERK signal pathways.

Elevated serum sortilin is related to carotid plaque concomitant with calcification.

Aim: To explore whether elevated serum sortilin was associated with calcified carotid plaque and ischemic stroke. Methods: A total of 171 patients with cardiovascular risk factors were enrolled. Ultrasonography was performed to evaluate calcified plaques and noncalcified plaques. Serum sortilin concentration was measured by ELISA. Results: Serum sortilin level was higher in patients with calcified carotid plaque and positively related to carotid plaque burden, but not with ischemic stroke during the follow-up. Multivariable logistic regression analysis revealed serum sortilin level was an independent determinant for calcified carotid plaque (p = 0.001). Receiving operating characteristic analysis showed an area under the curve of sortilin for carotid calcification was 0.759. Conclusion: Higher serum sortilin level was associated with carotid calcification and severe carotid plaque score.

Shock Index on Admission Is Associated with Coronary Slow/No Reflow in Patients with Acute Myocardial Infarction Undergoing Emergent Percutaneous Coronary Intervention.

OBJECTIVE: Coronary slow/no reflow is not rare after successfully undergoing primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI), and shock index (SI) is an important factor for adverse cardiovascular prognosis. In this study, we are to explore whether SI is associated with coronary slow/no reflow in patients with AMI following primary PCI. METHODS: A total of 153 consecutive AMI patients undergoing primary PCI within 24 hours of symptom onset were included in this study. The participants were divided into normal flow group (n=124) and slow/no reflow group (n=29) according to cineangiograms recorded during the period of PCI. Cardiovascular risk factors, hematologic parameters, preoperative management of antithrombotic therapy, and baseline angiography were collected. RESULTS: SI, plasma glucose, white blood cells (WBC) and neutrophil count, neutrophil to lymphocyte ratio (PLR), high sensitivity C-reactive protein (hs-CRP), probrain natriuretic peptide (pro-BNP), and Killip classification on admission and thrombus burden on initial angiography were significantly different between patients with and without slow/no reflow. Multivariate analysis revealed that SI≥0.66, thrombus burden, and plasma glucose on admission were independent predictors for coronary slow/no reflow. Preoperative management of tirofiban therapy improves initial thrombolysis in myocardial infarction (TIMI). However, it has no effect on prognosis of slow/no reflow. CONCLUSION: Our findings demonstrated that slow/no reflow in patients with AMI following primary PCI was more likely associated with SI≥0.66, thrombus burden, and plasma glucose on admission. SI as a predictor for coronary slow/no reflow should be further confirmed in the following more large-scale and prospective studies. The clinical registration number is ChiCTR1900024447.

YKL-40 promotes the progress of atherosclerosis independent of lipid metabolism in apolipoprotein E-/- mice fed a high-fat diet.

YKL-40 is recently regarded as a pro-inflammatory cytokine involved in the pathological process of atherosclerosis and lipid metabolism. However, whether YKL-40 can directly influence the development of atherosclerosis and levels of lipid parameters is unknown. The aim of this study is to explore the effects of YKL-40 on atherosclerotic features, the levels of serum lipids, and biomarkers in apolipoprotein (E)-deficient (ApoE-/-) mice fed a high-fat diet. ApoE-/- mice were injected with a recombinant adenovirus expressing mouse YKL-40 or control adenovirus through the caudal vein. The levels of serum YKL-40, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and soluble vascular cell-adhesion molecule 1 (sVCAM-1) were measured by ELISA. Lipid metabolism parameters were measured using immunoturbidimetric assay. The size of plaque area in aorta was evaluated by Oil Red O and hematoxylin/eosin (HE) staining. The content of collagen fibers was stained with Masson, and the content of macrophages and smooth muscle cells (SMCs) in atherosclerotic lesions was investigated by immunohistochemistry. The serum levels of total cholesterol and triglycerides were similar between these two groups. Compared with the control, the levels of serum YKL-40, IL-6, TNF-alpha, MMP-9, plaque size, and macrophages in plaques were significantly increased in mice with adenovirus overexpressing YKL-40. However, the content of collagen fibers and SMCs was remarkably decreased in mice with adenovirus overexpressing YKL-40 than that in control. YKL-40 prompts the progress of atherosclerosis maybe involved with its role of pro-inflammation, but does not affect lipid metabolism in ApoE-/- mice fed a high-fat diet.

Panax notoginseng Saponins Regulate Macrophage Polarization under Hyperglycemic Condition via NF-κB Signaling Pathway.

Panax notoginseng saponins (PNS), the principal constituents derived from Panax notoginseng, have been extensively used for treating cardiocerebral vascular diseases in China and other Asian countries. The main effects of PNS were anti-inflammatory properties, inhibition of platelet aggregation, improvement of blood flow and insulin resistance, and so on. This study was carried out to explore the effects of PNS on macrophage polarization under hyperglycemic conditions. Human acute monocyte leukemia cell line THP-1 cells were induced into macrophages with Phorbol ester (PMA). Macrophages were then divided into five groups as follows: control (5.5mMol/l glucose), hyperglycemia group (15mMol/l glucose), hyperglycemia plus low-dose PNS (20ug/ml), hyperglycemia plus moderate-dose PNS (40ug/ml), and hyperglycemia plus high-dose PNS (60ug/ml). After 48-hour cell culture, the percentages of M1- and M2-polarized macrophages were measured by flow cytometry analysis. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate the Ym1 and arginase 1 expression in macrophages. Protein expression of arginase 1, NF-κB p50, p65, and inhibitor of κB (IκB) alpha phosphorylation in macrophages was identified with Western blotting. PNS, especially the high-dose PNS, remarkably increased M2 phenotype ratio in macrophages cultured with hyperglycemia, and the mRNA expression of Ym1 and arginase 1 in macrophages was also upregulated. Meanwhile, PNS remarkably increased the protein expression of arginase 1 and decreased IκB-alpha phosphorylation and subunits of NF-κB p50 and p65 from macrophages in culture medium with hyperglycemia. Taken together, our work demonstrated that PNS promote macrophages to transform M2 phenotype under hyperglycemic conditions through downregulating NF-κB signaling pathway.

Proximal complete occlusion of right coronary artery presenting with precordial ST-segment elevation: A case report.

BACKGROUND: It is well known that cardiologists empirically judge the culprit lesion of acute ST-segment elevation myocardial infarction (STEMI) according to the corresponding electrocardiographic leads. However, In addition to the obstruction of left anterior descending (LAD) coronary artery, rare cases with the occlusion of proximal right coronary artery (RCA) and/or isolated right ventricular (RV) branch showed the ST-segment elevation in precordial leads V1-V3 as well. CASE SUMMARY: We reported a patient complaining of acute chest pain and suffering ventricular fibrillation (VF) on admission. The electrocardiogram (ECG) showed mild ST-segment elevation in precordial leads V1-V3 and V4R. Bedside echocardiography displayed normal left ventricular ejection fraction and slight RV dilation. Proximal occlusion of nondominant RCA was confirmed by coronary angiography and urgent percutaneous coronary intervention (PCI) to RCA successfully resolved the chest pain and ST-segment elevation. CONCLUSION: Undoubtedly, coronary angiography is usually the definite measurement for the diagnosis of culprit lesion. However, bedside echocardiography, ST-segment features in left and right precordial leads, and heart rate will be the additional information for judging ST-segment elevation in precordial leads V1-V3 resulting from occlusion of RCA or LAD.