関: 血管新生

plasminogenの分解産物

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/09 19:54:29」(JST)

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Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor (i.e., it blocks the growth of new blood vessels), and it is currently undergoing clinical trials for its use in anticancer therapy.^[1]

Structure[edit]

Angiostatin is a 38 kDa fragment of a larger protein, plasmin (itself a fragment of plasminogen) enclosing three to five contiguous Kringle modules. Each module contains two small beta sheets and three disulfide bonds.^[2]^[3]

Generation[edit]

Angiostatin is produced, for example, by autoproteolytic cleavage of plasminogen, involving extracellular disulfide bond reduction by phosphoglycerate kinase. Furthermore, angiostatin can be cleaved from plasminogen by different metalloproteinases (MMPs), elastase, prostate-specific antigen (PSA), 13 KD serine protease, or 24KD endopeptidase.

Biological activity[edit]

Angiostatin is known to bind many proteins, especially to angiomotin and endothelial cell surface ATP synthase but also integrins, annexin II, C-met receptor, NG2 proteoglycan, tissue-type plasminogen activator, chondroitin sulfate proteoglycans, and CD26. Additionally, smaller fragments of angiostatin may bind several other proteins. There is still considerable uncertainty on its mechanism of action, but it seems to involve inhibition of endothelial cell migration,^[4] proliferation and induction of apoptosis. It has been proposed that angiostatin activity is related, among other things, to the coupling of its mechanical and redox properties.^[5]

References[edit]

^ Safety and Efficacy Study of rhAngiostatin Administered in Combination With Paclitaxel and Carboplatin to Patients With Non-Small-Cell Lung Cancer - Full Text View - ClinicalTrials.gov
^ Cao Y, Ji RW, Davidson D, et al. (November 1996). "Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells". The Journal of Biological Chemistry 271 (46): 29461–7. doi:10.1074/jbc.271.46.29461. PMID 8910613. Retrieved 2009-06-18.
^ O'Reilly MS, Holmgren L, Shing Y, et al. (October 1994). "Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma". Cell 79 (2): 315–28. doi:10.1016/0092-8674(94)90200-3. PMID 7525077.
^ Redlitz A, Daum G, Sage EH (1999). "Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells". Journal of Vascular Research 36 (1): 28–34. doi:10.1159/000025623. PMID 10050071.
^ Grandi F, Sandal M, Guarguaglini G, Capriotti E, Casadio R, Samorì B (November 2006). "Hierarchical mechanochemical switches in angiostatin". Chembiochem : a European Journal of Chemical Biology 7 (11): 1774–82. doi:10.1002/cbic.200600227. PMID 16991168.

External links[edit]

Angiostatins at the US National Library of Medicine Medical Subject Headings (MeSH)

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UpToDate Contents

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1. 血管新生阻害剤の概要 overview of angiogenesis inhibitors
2. 進行非小細胞肺癌に対する研究試験治療 investigational approaches for advanced non small cell lung cancer
3. 全身性硬化症（強皮症）の病因 pathogenesis of systemic sclerosis scleroderma
4. 疾患状態における冠微小循環 the coronary microcirculation in disease states
5. 悪性神経膠腫に対する実験的治療アプローチ experimental treatment approaches for malignant gliomas

English Journal

Endogenous angiogenesis inhibitors prevent adaptive capillary growth in left ventricular pressure overload hypertrophy.

Nikolova A, Ablasser K, Wyler von Ballmoos MC, Poutias D, Kaza E, McGowan FX, Moses MA, Del Nido PJ, Friehs I.SourceDepartment of Cardiac Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA.
The Annals of thoracic surgery.Ann Thorac Surg.2012 Nov;94(5):1509-17. doi: 10.1016/j.athoracsur.2012.05.052. Epub 2012 Jul 12.
BACKGROUND: In left ventricular (LV) pressure-overload hypertrophy, lack of adaptive capillary growth contributes to progression to failure. Remodeling of the hypertrophied myocardium requires proteolysis of the extracellular matrix (ECM) carried out by matrix metalloproteinases (MMPs). MMPs, specif
PMID 22795062

Endorepellin affects angiogenesis by antagonizing diverse VEGFR2-evoked signaling pathways: transcriptional repression of HIF-1α and VEGFA and concurrent inhibition of NFAT1 activation.

Goyal A, Poluzzi C, Willis CD, Smythies J, Shellard A, Neill T, Iozzo RV.SourceThomas Jefferson University, United States.
The Journal of biological chemistry.J Biol Chem.2012 Oct 11. [Epub ahead of print]
Endorepellin, the angiostatin C-terminal domain of the heparan sulfate proteoglycan perlecan, inhibits angiogenesis by simultaneously binding to the α2β1 integrin and the VEGF receptor 2 (VEGFR2) on endothelial cells. This interaction triggers the downregulation of both receptors and the concurren
PMID 23060442

Japanese Journal

Nicked β2-Glycoprotein I と Angiostatin Kringle 1-4.5 の血管新生に与える影響

中川久子,保田晋助,松浦栄次,小林和子,家子正裕,片岡浩,堀田哲也,渥美達也,小池隆夫
日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis 21(3), 314-318, 2010-06-01
NAID 10026400495

Angiostatin Inhibition of Vascular Endothelial Growth Factor-Stimulated Nitric Oxide Production in Endothelial Cells

TAKAHASHI Satoru,SHINYA Tomohiro,SUGIYAMA Akinori
Journal of pharmacological sciences 112(4), 432-437, 2010-04-20
… Angiostatin (AS), a proteolytic fragment of plasminogen, is a potent antiangiogenic factor. …
NAID 10027909085

Related Pictures

★リンクテーブル★

リンク元	「血管内皮増殖因子」「成長因子」「bFGF」「endostatin」「血管新生」

「血管内皮増殖因子」

　　[★]

英: vascular endothelial growth factor, VEGF
同: 血管内皮細胞増殖因子、vascular endothelial cell growth factor
関: 血管新生

[show details]

血管内皮細胞増殖因子 : 約 33,200 件
血管内皮増殖因子 : 約 503,000 件

血管内皮増殖因子 : 約 93 件
血管内皮成長因子 : 約 81 件

癌における血管新生に関与している (同：VEGF。対：angiostatin, endostatin, vasculostatin)
標的は血管内皮細胞のみ
腫瘍や心臓や網膜の虚血部位で過剰に産生される。
低酸素状態にさらされた組織で過剰に産生される。

「成長因子」

　　[★]

英: 成長因子 growth factor
同: 成長促進因子 growth-promoting substance、発育因子、増殖因子

[show details]

発育因子 : 約 8,070 件
成長因子 : 約 675,000 件
増殖因子 : 約 1,290,000 件

発育因子 growth : 約 12,100 件
成長因子 growth : 約 319,000 件
増殖因子 growth : 約 157,000 件

TGF-β
PDGF

血管新生

angiogenic factor

VEGF
bFGF

angiostasis

「bFGF」

　　[★]

英: basic FGF, basic fibroblast growth factor
同: FGF-2 塩基性線維芽細胞成長因子
関: FGF fibroblast growth factor

癌における血管新生に関与している (同：VEGF。対：angiostatin, endostatin, vasculostatin)
細胞間マトリックスに蓄えらているbFGFはプロテアーゼによって放出される (BPT.201)
mitogenである：mesenchymall, neural, and epithelial organ

「endostatin」

　　[★]

関: 血管新生、コラーゲン

XVIII型コラーゲンの分解産物
angiostatic factor(anti-angiogenesis)

angiogenic factors such as VEGF and bFGF have relatively long half-lives in the blood compared with angiostatic factos such as endostain or angiostatin.

large tumors often produce sufficient amounts of angiostatic factors to suppress the growth of blood vessels in small, undetectable tumors present elsewhere in the body.

「血管新生」

　　[★]

英: angiogenesis
同: 二次血管発生
関: 脈管形成 vasculogenesis

既存の血管から芽が出て新たな血管が形成される

==血管新生促進

bFGF FGF-2
VEGF

血管新生抑制

[1] Safety and Efficacy Study of rhAngiostatin Administered in Combination With Paclitaxel and Carboplatin to Patients With Non-Small-Cell Lung Cancer - Full Text View - ClinicalTrials.gov

[2] Cao Y, Ji RW, Davidson D, et al. (November 1996). "Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells". The Journal of Biological Chemistry 271 (46): 29461–7. doi:10.1074/jbc.271.46.29461. PMID 8910613. Retrieved 2009-06-18.

[3] O'Reilly MS, Holmgren L, Shing Y, et al. (October 1994). "Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma". Cell 79 (2): 315–28. doi:10.1016/0092-8674(94)90200-3. PMID 7525077.

[4] Redlitz A, Daum G, Sage EH (1999). "Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells". Journal of Vascular Research 36 (1): 28–34. doi:10.1159/000025623. PMID 10050071.

[5] Grandi F, Sandal M, Guarguaglini G, Capriotti E, Casadio R, Samorì B (November 2006). "Hierarchical mechanochemical switches in angiostatin". Chembiochem : a European Journal of Chemical Biology 7 (11): 1774–82. doi:10.1002/cbic.200600227. PMID 16991168.

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案内

案内

angiostatin