Clinical Effection On Abnormal Expression Of The Angiopoietin-1&-2 And Receptor Tie-2 In Human Intracranial Aneurysms

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) are vascular lesions that often present as cerebral hemorrhage in adults. Human intracranial aneurysms (ICA) are associated with endothelial activation. Angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2) are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of angiopoietins levels as biomarkers of disease in human intracranial aneurysms.ObjectiveTo investigate the effect of the levels of Ang-1, Ang-2 and Tie-2 in ICA.MethodsWe carried out a free ICA screening in Tianjin.41 patients with ruptured (n=36) and unruptured (n=5) ICA and 40 healthy control subjects were recruited from December 2009 to June 2010. All the patients were diagnosed by CTA or DSA. And the operations were carried outPart ASerum samples were collected as follows:40 from control subjects,41 from patients with ICA. Serum levels of Ang-1, Ang-2 and receptor Tie-2 were tested by enzymelinked immunosorbent assay (ELISA), and compared between patients with ICA and control subjects by statistical methods. The levels of serum Ang-1,Ang-2 and Tie-2 in the patients of Hunt-HessⅠ～Ⅴwere measured.Part BSerum samples were collected as follows:15 from patients with hypertensive cerebra 1 hemorrhage (ICH),20 from patients with aSAH. Serum levels of Angl, Ang2 and Tie-2 of all patients in Od,7d and 21d were tested by enzymelinked immunosorbent assay (ELISA) and compared patients with aSAH and patients with ICH by statistical methods.Part CPathological samples were collected as follows:12 of normal blood vessels,21 of ICA.The expression of Angl, Ang2, Tie-2 and structural changes in ICAs were observed with immunohistochemistry and microscopic technique respectively. The levels of Ang-1, Ang-2 and receptor Tie-2 were tested, and compared between patients with ICA and normal blood vessels by statistical methods.Results1. The levels of serum Ang-1 (t=8.344, P=0.000), Ang-2 (t=2.289, P=0.025), Tie-2 (t=2.481, P=0.015), SBP (t=10.154,P=0.000) and DBP (t=5.905,P=0.000) of ICA patients had significant higher levels, when compared with control subjects.2. The levels of serum Ang-1 (t=-6.497, P=0.000), Ang-2 (t=-4.405,P=0.000) and DBP (t=-2.162, P=0.038) in the patients of aSAH Hunt-HessⅠ～Ⅲwere significantly lower than them of aSAH Hunt-Hess IV-V.3. The tendency levels of serum Ang-1 (Ftime=83.457) and Ang-2 (F time=8.029) in the patients of aSAH were significantly higher than them of ICH in Od,7d and 21d (P<0.05).4. Endothelial cells of ICAs were degenerated and collaped and a number of vesicles and swollen mitochondria were present in the cytoplasm. The ICA wall varied in thickness and was composed of regenerative smooth muscle cells and collagenous fibres.5. Ang-1 (t=-28.034, P=0.000), Ang-2 (t=6.238, P=0.000) and a-SMA (t=-13.067, P=0.000) was overexpressed in ICAs, when compared with that of normal blood vessels.Conclusions1. The expression of Ang-1, Ang-2 and receptor Tie-2 and vascular degenerative changes might play an important role in the pathogenesis and rupture of ICAs.2. A novel hypothesis in the formation and progression of ICAs has been proposed.3.These results suggest that serum Ang-1 and Ang-2 levels are promising clinically informative biomarkers of disease severity in aSAH.