Angiopoietin-2 Polymorphism In Chinese Hemorrhagic Stroke

Angiopoietin-2 Polymorphism in Chinese Hemorrhagic StrokeStroke is the second leading cause of death and the first cause of disability in China. Multiple factors, including genetic and environmental, contribute to the development of this disease. Hemorrhagic stroke takes 21%~48% of total stroke in Chinese, two to three times higher than that in Caucasian population. The cause for this disease remains unknown. It is generally accepted that hypertension, atherosclerosis, malformation of cerebral vessels, infections are the risk factors for hemorrhagic stroke in a quantitative pattern. The difference in hemorrhagic stroke incidence between Chinese and Caucasians may be due to the difference between environmental or genetic risk factors in these two populations.Angiopoietin-2 (Ang2), a natural antagonist to Tie2 receptor, modulates angiogenesis and vasculogenesis in a constitutive and context-dependent way. Gene knockout model of Ang2 showed that animals died in the later stage of angiogenesis due to leakage of vessel and edema of peripheral tissue. The integrity of vessels might be destroyed and the permeability of vessels may increase due to dysfunction of Ang2. Besides, Ang2 can prime endothelial cells to angiogenesis and requisite for postnatal vascular remodeling. Since edema and leakage are very common in hemorrhage stroke and elevated expression of Ang2 were identified in stoke-prone spontaneously hypertensive rat (SHRSP) and middle cerebral artery occlusion (MCAO), we can hypothesize with confidence that dysfunction of Ang2 may be involved in stroke. Monoclonal antibodies (mAb) against vessel growth factors have been widely used in diagnosis and therapy of angiogenesis related diseases. MAb against Ang2 will show its usefulness in: 1) powerful tool in mechanism study of Ang2's role in hemorrhage stroke, 2) neutralizing antibody or drug/toxin carrier for therapy of vascularized diseases (tumors, retinopathy diabetes, etc.). In order to make the mAb against human Ang2, we constructed an immunized mouse single chain Fv (scFv) antibody library...