Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen, nutrients, and other essential factors. The well?known vascular endothelial growth factor (VEGF) signaling is crucial for sprout?ing angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature, which has become therapeutic targets in clinical practice. However, the survival beneifts gained from targeting VEGF signal?ing have been very limited, with the inevitable development of treatment resistance. In this article, we discuss the most recent ifndings and understanding on how solid tumors evade VEGF?targeted therapy, with a special focus on vessel co?option, vessel remodeling, and tumor cell?derived vasculature establishment. Vessel co?option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth. The differences between vessel?like structure and tubule?like structure formed by tumor cells are also intro?duced. The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.

Objective:To compare the effects of different doses of ticagrelor on microcirculation, inflammatory factors and cardiac function in older adult patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:A total of 250 older adult patients with coronary heart disease who received PCI in The First People's Hospital of Wenling, China between March 2019 and March 2020 were included in this study. They were randomly assigned into group A and group B, with 125 patients per group. The group A was subjected to staged exercise and oral ticagrelor (45 mg once, twice a day). The group B was given staged exercise and oral ticagrelor (90 mg once, twice a day). Platelet function (maximum platelet aggregation rate, P2Y12 reaction unit), microcirculation (the index of microcirculatory resistance, circulatory flow reserve), inflammatory factor levels (high-sensitivity C-reactive protein, tumor necrosis factor alpha, interleukin-6), cardiac function recovery (left ventricular ejection fraction, 6-minute walk test, maximal oxygen consumption), cardiovascular adverse events, and bleeding events were compared between the two groups.Results:After treatment, maximum platelet aggregation rate and P2Y12 reaction unit in group B were (28.79 ± 3.52)% and (132.36 ± 12.16) U, respectively, which were significantly lower than those in group A [(33.45 ± 4.60)%, (146.79 ± 13.52) U, t = 8.99, 8.87, both P < 0.001]. After treatment, the index of microcirculatory resistance in group B was significantly lower than that in group A [(26.43 ± 4.51) vs. (29.68 ± 5.14), t = 5.31, P < 0.001]. Circulatory flow reserve in group B was significantly higher than that in group A [(2.16 ± 0.62) vs. (1.61 ± 0.50), t = 7.72, P < 0.001]. After treatment, tumor necrosis factor alpha, interleukin-6 and high-sensitivity C-reactive protein in group B were (39.54 ± 6.74) ng/L, (19.68 ± 4.06) ng/L, (5.98 ± 1.35) mg/L, respectively, which were significantly higher than those in group A [(28.26 ± 6.15) ng/L, (15.33 ± 3.87) ng/L, (4.83 ± 1.28) mg/L, t = 13.82, 8.67, 6.91, all P < 0.001]. After treatment, left ventricular ejection fraction, 6-minute walk test, maximal oxygen consumption in group B were (37.39 ± 5.10)%, (443.28 ± 29.64) m, (19.69 ± 3.57) L/min, respectively, which were significantly higher than those in group A [(34.64 ± 4.86)%, (410.45 ± 25.76) m, (17.33 ± 3.27) L/min, t = 4.36, 9.34, 5.45, all P < 0.001]. There was no significant difference in total incidence of cardiovascular events between the two groups (χ 2 = 0.05, P > 0.05). The incidence of bleeding events in group A was significantly lower than that in group B (4.80% vs. 13.60%, χ 2 = 5.79, P < 0.05). Conclusion:Compared with ticagrelor 90 mg/d, ticagrelor 180 mg/d can more greatly improve platelet function and microcirculation, reduce inflammatory reaction, promote the recovery of cardiac function, and reduce bleeding events in older adult patients with coronary heart disease after percutaneous coronary intervention.