PMID- 28272703 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20170727 LR - 20180322 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 21 IP - 4 DP - 2017 Feb TI - The study of endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms. PG - 795-803 LID - 12244 [pii] AB - OBJECTIVE: Inflammation as a significant influence factor plays an important role in the formation and rupture of intracranial aneurysms. However, based on plenty of related studies, it is believed that the hepatocyte growth factor (HGF) is able to prevent vascular inflammation. This paper, therefore, explored the role and mechanism of endogenous HGF in the pathogenesis of intracranial aneurysms. MATERIALS AND METHODS: 16 blood samples were collected from the intracranial aneurysms and the lumens of the femoral artery of 16 patients. Comparison and quantitative detection of HGF serum concentrations in an aneurysm and femoral artery samples according to the immune assay based on Luminex were followed. The tissue of superficial temporal artery (STA) and ruptured or unruptured intracranial aneurysm from the patients (n=10) who were performed surgical clipping of craniotomy was then collected. The intracranial aneurysm model was induced by surgery on adult c57/B16 mouse and grouping administration of c-Met antagonist PF-04217903 or its solvent DMSO for 3 weeks. Then, the brains of the experimental mouse were dissected and examined whether there were intracranial aneurysms and/or subarachnoid hemorrhage (SAH). The procedures followed by treatment of human endothelial cells cultured in vitro, smooth muscle cells and monocytes with HGF and PF-04217903 lipopolysaccharide (LPS). Through Real-time fluorescence quantitative PCR, with DeltaDeltaCt methods, we used the expressions of beta-actin normalized inflammatory factor [intercellular adhesion molecule-1 (ICAM-1)], vascular cell adhesion molecule-1 (VCAM-1), E-selectin, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and transforming growth factor-beta (TGF-beta). RESULTS: It was found that the concentration of HGF (1076+/-656) pg/ml from the blood collected from human intracranial aneurysms was significantly higher than that from the femoral artery (196+/-436) pg/ml (p<0.01). Experimental mouse treated with PF-04217903 (c-Met antagonist) and in control group were induced to form intracranial aneurysms. C-Met antagonists did not alter the formation of intracranial aneurysms (p>0.05), but significantly increased the occurrence of subarachnoid hemorrhage and reduced the survival rate of mice (p<0.05). HGF attenuated the expression of VCAM-1 (p<0.05) and E-selectin (p<0.05) in human aortic endothelial cells CONCLUSIONS: The plasma HGF levels were elevated in intracranial aneurysms, and the HGF and c-Met were expressed in STA and intracranial aneurysms. In the treatment of intracranial aneurysms, HGF signaling pathway reduced inflammation in endothelial cells and prevented the rupture of intracranial aneurysm through c-Met. FAU - Yu, L-L AU - Yu LL AD - Department of Neurosurgery, Qingdao Hiser Medical Center, Qingdao, Shandong, China. jbaad410@sina.com. FAU - Liu, Y-J AU - Liu YJ FAU - Wang, Z-H AU - Wang ZH FAU - Shi, L AU - Shi L FAU - Liu, L-X AU - Liu LX LA - eng PT - Journal Article PT - Retracted Publication PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RIN - Eur Rev Med Pharmacol Sci. 2017 Mar;21(6):1176. PMID: 28387918 EDAT- 2017/03/09 06:00 MHDA- 2017/03/09 06:01 CRDT- 2017/03/09 06:00 PHST- 2017/03/09 06:00 [entrez] PHST- 2017/03/09 06:00 [pubmed] PHST- 2017/03/09 06:01 [medline] AID - 12244 [pii] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2017 Feb;21(4):795-803.