Intravenous transfusion of endothelial colony-forming cells attenuates vascular degeneration after cerebral aneurysm induction

• Published in: Brain research Vol. 1593; pp. 65 - 75
• Main Authors: Li, Shengjie, Tian, Ye, Huang, Xintao, Zhang, Yongqiang, Wang, Dehui, Wei, Huijie, Dong, Jingfei, Jiang, Rongcai, Zhang, Jianning
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17.12.2014; Elsevier
• Subjects: Animals; Anterior Cerebral Artery; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell- and Tissue-Based Therapy - methods; Cells, Cultured; Cerebral aneurysm; Chemokine CCL2 - metabolism; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial colony-forming cells; Endothelial Progenitor Cells - transplantation; Fundamental and applied biological sciences. Psychology; Inflammation; Intracranial Aneurysm - pathology; Intracranial Aneurysm - physiopathology; Intracranial Aneurysm - therapy; Macrophage; Macrophages - pathology; Macrophages - physiology; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - physiopathology; Neurology; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Random Allocation; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transfusion; Vascular Cell Adhesion Molecule-1 - metabolism; Vertebrates: nervous system and sense organs; eNOS; TIMP-1; least significant difference; Transfusion; internal elastic lamina; phosphate-buffered solution; diI-acetylated low-density lipoprotein; mononuclear cells; NF-κB; ECFCs; ECs; RT-PCR; KDR; endothelial nitric oxide synthase; anterior cerebral artery/olfactory artery; UEA-1-FITC; LSD; matrix metalloproteinases; PBS; left common carotid artery; cerebral aneurysm; real-time reverse transcription polymerase chain reaction; kinase domain receptor; smooth muscle cells; ulex europaeus agglutinin-1 labeled with fluorescein isothiocyanate; IEL; LCCA; ACA/OA; B-cell leukemia/lymphoma-2; Macrophage; Bcl-2; endothelial cells; MCP-1; vWF; NS; nuclear factor kappa B; SMCs; macrophage chemoattractant protein-1; MNCs; ANOVA; endothelial progenitor cells; DiI-acLDL; VE-cadherin; EPCs; tissue inhibitors of metalloproteinases-1; CA; vascular endothelial cadherin; one-way analysis of variance; endothelial colony-forming cells; MMPs; Inflammation; normal saline; von willebrand factor; Apoptosis; Cerebral aneurysm; Endothelial colony-forming cells; Endothelial cell; Intravenous administration; Induction; Central nervous system; Aneurysm; Cardiovascular disease; Colony forming cell; Encephalon; Vascular disease; Cell death; Degeneration
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2014.09.077

Abstract Cerebral aneurysm (CA) rupture is a major cause of subarachnoid hemorrhage with high morbidity and mortality. Using an animal model, we examined the potential of endothelial colony-forming cells (ECFCs) transfusion on vascular degeneration after CA induction and underlying mechanisms. CA was induced in the right anterior cerebral artery–olfactory artery (ACA/OA) bifurcations in Sprague–Dawley rats with or without ECFCs transfusion. The degeneration of internal elastic lamina (IEL), media thickness and CA size were evaluated. Expression of matrix metalloproteinase-2 and 9 (MMP-2 and 9), tissue inhibitor of metalloproteinase-1 (TIMP-1), macrophage chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor κB (NF-κB), endothelial nitric oxide synthase (eNOS), B-cell leukemia/lymphoma-2 (Bcl-2), and inducible nitric oxide synthase (iNOS) were analyzed by quantitative real-time polymerase chain reaction. The macrophages infiltration and apoptosis of smooth muscle cells (SMCs) were examined immunohistologically. Rats in CA+ECFCs transfusion group showed a notable reduction in IEL degeneration, media thinning and CA size compared with those in CA+saline group. ECFCs transfusion inhibited the MMP-driven wall destruction by downregulating MMP-2, MMP-9 expression and upregulating TIMP-1. ECFCs transfusion dramatically decreased VCAM-1 and NF-κB expression, increased eNOS expression and caused no change in MCP-1 expression, which was accompanied by reduced macrophages infiltration. Moreover, ECFCs transfusion reversed downregulation of Bcl-2 expression and upregulation of iNOS expression, and decreased SMCs apoptosis. Collectively, these findings suggest that ECFCs transfusion confers protection against degeneration of aneurysmal wall by inhibiting inflammatory cascades and SMCs apoptosis.