title: Tryptase promotes atherosclerotic plaque haemorrhage in ApoE-/- mice.
abstract: Tryptase, the most abundant mast cell (MC) granule protein, plays an important role in atherosclerosis plaque development. To test the hypothesis that tryptase participates directly in atherosclerosis plaque haemorrhage, the gene sequence and siRNA for tryptase were cloned into a lentivirus carrier and atherosclerosis plaque haemorrhage models in ApoE-/- mice were constructed. After a cuffing-cervical artery operation, the mice were randomly divided into 6 groups. Hematoxylin and eosin(HE) staining showed that the cervical artery plaque area was much larger in the tryptase overexpression group compared to the other groups, and there was greater artery stenosis. The artery stenosis from the cuff-side in all groups was more than 90%, except the siRNA group. Tryptase promotes plaque haemorrhage distinctively because 50% of the mice in the tryptase overexpression group had plaque haemorrhage, while only 10% in the siRNA group did. The immunohistochemistry of the cervical artery plaque showed that plasminogen activator inhibitor-1 (PAI-1) expression was the lowest while tissue plasminogen activator (tPA), CD31, CD34 and VEGF was the highest in the tryptase overexpression groups. This observation was completely contrary to what was observed in the siRNA group. Tryptase promoted bEnd.3 cell growth, migration and capillary-like tube formation, which suggests that tryptase can promote microvessel angiogenesis. PAI-1 expression was inhibited, while tPA expression was increased by tryptase in bEnd.3 cells. Our in vivo and in vitro studies suggest that trypase can promote atherosclerotic plaque haemorrhage by promoting angiogenesis and regulating the balance of PAI-1 and tPA. Thus, regulating tryptase expression in MCs may provide a potential target for atherosclerosis treatment.
authors.affiliation: Laboratory of Medical Molecular Biology, Teaching Center of Experimental Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Zhi
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Dai
authors.initials: D
authors.lastname: Tian
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Ning
authors.forename: Lianhua
authors.initials: L
authors.lastname: Yin
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006470:Hemorrhage / Q000201:enzymology*; D016086:Lentivirus / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D058258:Serpin E2 / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D053802:Tryptases / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D001057:Apolipoproteins E; D008055:Lipids; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053802:Tryptases; D010959:Tissue Plasminogen Activator