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Higher serum angiopoietin 2 levels are independently associated with coronary microvascular dysfunction in patients with angina in the absence of obstructive coronary artery disease

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Chinese Medical Journal 2020年第14期133卷 1662-1668页

作者： Shao-Min Chen Dan Li Xing Xing Zhao-Ping Li Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalKey Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesMinistry of HealthKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China Department of Cardiovascular Medicine Beijing First Hospital of Integrated Chinese and Western MedicineBeijing 100039China.

Background:angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular *** Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive ***:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional *** flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler *** patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values2.5 and the preserved CFR group with CFR values≥*** Ang-2 levels were determined using enzyme-linked immunosorbent *** predictors for impaired CFR were identified by binary logistic regression *** receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired ***:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P2 levels were negatively correlated with CFR(r=0.386,P2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired ***,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P2(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.

关键词： Coronary microvascular dysfunction angiopoietin 2 Coronary flow reserve

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Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer

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World Journal of Gastroenterology 2016年第27期22卷 6287-6295页

作者： Amalia Azzariti Letizia Porcelli Oronzo Brunetti Marzia Del Re Vito Longo Patrizia Nardulli Michele Signorile Jian-Ming Xu Angela Calabrese Anna Elisa Quatrale Evaristo Maiello Vito Lorusso Nicola Silvestris Clinical and Preclinical Pharmacology Laboratory National Cancer Research Centre Istituto Tumori Giovanni Paolo II 70124 Bari Italy Medical Oncology Unit National Cancer Research Centre Istituto Tumori Giovanni Paolo II 70124 Bari Italy Clinical Pharmacology and Pharmacogenetics Unit Department of Clinical and Experimental Medicine University Hospital 56126 Pisa Italy Pharmacology Unit National Cancer Research Centre Istituto Tumori Giovanni Paolo II 70124 Bari Italy Department of Gastrointestinal Oncology Affiliated Hospital Cancer Center Academy of Military Medical Sciences Beijing 100071 China Radiology unit National Cancer Research Centre Istituto Tumori Giovanni Paolo II 70124 Bari Italy Medical Oncology Unit 'Casa Sollievo della Sofferenza' Hospital 71013 San Giovanni Rotondo Italy Medical Oncology Unit 'Mons R Dimiccoli' Hospital 76121 Barletta Italy

AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.

关键词： Bevacizumab Vascular endothelial growth factor angiopoietin 2 Metastatic colorectal cancer Biomarker Predictive factor

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