title: Adenoviral gene transfer of viral interleukin-10 protects cerebrovascular impairment induced by lysophosphatidylcholine.
abstract: Cerebrovascular disease is a significant cause of morbidity and mortality in the world. Inflammatory processes induce several pathological responses such as atherosclerosis, which have fundamental roles in stroke in the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. Viral interleukin-10 (vIL-10), a potential anti-inflammatory cytokine, has been studied extensively. However, the efficacy of vIL-10 on cerebrovascular dysfunction is not well known. Our goal in this study was to explore the effect of gene transfer of vIL-10 mediated by adenovirus (Ad/vIL-10) on cerebrovascular function using a model of vasocontraction of isolated basilar artery from mongrel dogs induced by lysophosphatidylcholine (lysoPC), a proinflammatory and atherogenic serum lysophospholipid. To clarify the relation between contraction of basilar aorta and cell adhesion and adhesion molecules, our further study explored effects of Ad/vIL-10 on monocyte-cerebrovascular endothelial cells adhesion and expression of cell adhesion molecule by cultured cerebromicrovascular endothelial cells, bEnd.3, after incubation by lysoPC. Our results showed that Ad/vIL-10 significantly decreased contractive response of basilar aorta produced by lysoPC and augmented vasorelaxation to acetylcholine. Further studies showed the Ad/vIL-10 significantly depressed adherence of monocytes to cerebrovascular endothelial cells and inhibited up-regulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are bio-markers in inflammatory progress. These data demonstrated the protective effects of Ad/vIL-10 on cerebrovascular dysfunction induced by inflammation, and proved that inhibition of expression of cell adhesion molecules should be one of ways of vIL-10 to protect vascular function during inflammation.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, No.325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Yang
authors.forename: Yao-Cheng
authors.initials: YC
authors.lastname: Rui
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001488:Basilar Artery / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D002560:Cerebrovascular Circulation / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000235:genetics*; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism; D018014:Gene Transfer Techniques; D066298:In Vitro Techniques; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000502:physiology; D008244:Lysophosphatidylcholines; D051379:Mice; D008833:Microcirculation / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction / Q000235:genetics
chemical_list: D008244:Lysophosphatidylcholines; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10