Inhibitory effect of recombinant human endostatin on angiogenesis in atherosclerotic plaque of rats by regulating Dll4/Notch pathway |
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| Authors: | CAI Hong-wen ZHU Min ZHOU Xin-bin MIAO Jing QIU Yuan-gang MAO Wei |
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| Institution: | Department of Cardiology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China |
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| Abstract: | AIM: To observe the inhibitory effect of recombinant human endostatin (rhES) on plaque angiogenesis, and to explore the regulatory mechanism of Dll4/Notch pathway in the anti-angiogenic effect of rhES. METHODS: Male Wistar rats were randomized into 3 groups:normal control group (N group), atherosclerotic model group (AS group), and rhES treated group (AS+rhES group). The rats in N group were fed a normal diet, while the remaining 2 groups were established to atherosclerotic rat model via high-cholesterol diet, intraperitoneal injection of vitamin D3 and aortic balloon injury. The rats in AS+rhES group received intraperitoneal injection of rhES. The blood total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-1 (IL-1) and troponin I (TnI) were measured. The atherosclerotic abdominal aortas were taken for pathological observation. Immunohistochemical staining was used to measure the density of neovessels in the plaques, which were marked by CD31. The protein levels of Dll4 and Notch1 in the aortas were analyzed by Western blot. RESULTS: The levels of blood TC, TG, LDL-C, CRP and IL-1 in AS group and AS+rhES group were much higher than those in N group (P<0.05), and no statistical difference between AS group and AS+rhES group was observed. The expression of CD31 in AS group was the highest among all groups. Compared with AS group, the density of neovessels in the plaques of AS+rhES group decreased significantly (P<0.05). The protein expression of Dll4 and Notch1 in AS group was lower than that in N group (P<0.05). Compared with AS group, the protein expression of Dll4 and Notch1 increased significantly (P<0.05). CONCLUSION: rhES has the ability to inhibit plaque angiogenesis in rats. The activation of Dll4/Notch pathway may be the mechanism of rhES in inhibiting plaque angiogenesis. |
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| Keywords: | Recombinant human endostatin Atherosclerosis Dll4/Notch pathway Angiogenesis |
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