組織プラスミノゲンアクチベータ, t-PA, tPA, plasmino gen activators, tissuetype

関: alteplase、Alteplase, Retavase

WordNet

a soft thin (usually translucent) paper (同)tissue_paper
part of an organism consisting of an aggregate of cells having a similar structure and function
(biology) any agency bringing about activation; a molecule that increases the activity of an enzyme or a protein that increases the production of a gene product in DNA transcription
an inactive form of plasmin that occurs in plasma and is converted to plasmin by organic solvents

PrepTutorEJDIC

〈U〉〈C〉(生物体の)『組織』 / 〈U〉〈C〉『薄織物』 / 〈U〉〈C〉水を吸収する柔らかな薄紙 / 〈C〉カーボンコピー用薄紙 / 〈C〉《a ~》(…を)織り交ぜて作ったもの《+of+名》 / =tissue paper

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/02/18 20:37:57」(JST)

wiki en

[Wiki en表示]

PLAT redirects here. It can also refer to the People's Liberation Army of Thailand.

Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. It is a serine protease (EC 3.4.21.68) found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine to treat embolic or thrombotic stroke. Use is contraindicated in hemorrhagic stroke and head trauma.

tPA may be manufactured using recombinant biotechnology techniques. tPA created this way may be referred to as recombinant tissue plasminogen activator (rtPA).

Function

A simplified illustration demonstrates clot breakdown (fibrinolysis), with blue arrows denoting stimulation, and red arrows inhibition.

tPA and plasmin are the key enzymes of the fibrinolytic pathway in which tPA mediated plasmin generation occurs. To be specific, tPA cleaves the zymogen, plasminogen at its Arg560 - Val561 peptide bond, into the serine protease plasmin.

Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding. Decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism.

Tissue plasminogen activator also plays a role in cell migration and tissue remodeling.

Genetics

Tissue plasminogen activator is a protein encoded by the PLAT gene, which is located on chromosome 8. The primary transcript produced by this gene undergoes alternative splicing, producing three distinct messenger RNAs.

Clinical applications

tPA is used in diseases that feature blood clots, such as pulmonary embolism, myocardial infarction, and stroke, in a medical treatment called thrombolysis. To be most effective in ischemic stroke, tPA must be administered as early as possible after the onset of symptoms. Protocol guidelines require its use intravenously within the first three hours of the event, after which its detriments may outweigh its benefits. They can either be administered systemically, in the case of acute myocardial infarction, acute ischemic stroke, and most cases of acute massive pulmonary embolism, or administered through an arterial catheter directly to the site of occlusion in the case of peripheral arterial thrombi and thrombi in the proximal deep veins of the leg.^[1] The guideline in Ontario, Canada hospitals for ischemic strokes is that tPA must be given within 4.5 hours of the onset of symptoms.^{[citation needed]} Because of this, only about 3% of patients qualify for this treatment, since most patients do not seek medical assistance quickly enough.^{[citation needed]} In the United States, the window of administration used to be 3 hours from onset of symptoms, but the newer guidelines also recommend use up to 4.5 hours after symptom onset.^[2] tPA appears to show benefit not only for large artery occlusions but also for lacunar strokes. Since tPA dissolves blood clots, there is risk of hemorrhage with its use.

tPA has also been given to patients with acute ischemic stroke above age 90 years old. Although a small fraction of patients 90 years and above treated with tPA for acute ischemic stroke recover, most patients have a poor 30-day functional outcome or die.^[3] Nonagenarians may do as well as octogenarians following treatment with IV-tPA for acute ischemic stroke.^[4] In addition, people with frostbite treated with tPA had fewer amputations than those not treated with tPA.^[5] In tPA overdose, aminocaproic acid works as an antidote.^[6]

Recombinant tissue plasminogen activators

Recombinant tissue plasminogen activators (r-tPAs) include alteplase, reteplase, and tenecteplase (TNKase).^[1]

Activase (Alteplase) is FDA-approved for treatment of myocardial infarction with ST-elevation (STEMI), acute ischemic stroke (AIS), acute massive pulmonary embolism, and central venous access devices (CVAD).^[1]

Reteplase is FDA-approved for acute myocardial infarction, where it has more convenient administration and faster thrombolysis than alteplase.^[1]

Tenecteplase is also indicated in acute myocardial infarction, showing fewer bleeding complications but otherwise similar mortality rates after one year compared to alteplase.^[1]

Additional r-tPAs, such as desmoteplase, are under clinical development.

Interactions

Tissue plasminogen activator has been shown to interact with Fibrinogen alpha chain,^[7]^[8] LRP1^[9]^[10] and SERPINI1.^[11]

References

^ ^a ^b ^c ^d ^e eMedicine Specialties > Thrombolytic Therapy Author: Wanda L Rivera-Bou; Coauthors: Jose G Cabanas and Salvador E Villanueva. Updated: Nov 20, 2008
^ Stroke 2009; 40: 2266-2267
^ Mateen FJ, Nasser M et al. (2009). "Outcomes of intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 90 years or older". Mayo Clin Proceedings. 84 (4): 384–8. doi:10.1016/S0025-6196(11)60542-9. PMC 2665978. PMID 19339651. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2665978/.
^ Mateen FJ, Buchan AM, Hill MD, for the CASES investigators (2010). "Outcomes of thrombolysis for acute ischemic stroke in octogenarians versus nonagenarians". Stroke. 41 (8): 1833–5. doi:10.1161/STROKEAHA.110.586438. PMID 20576948. http://www.ncbi.nlm.nih.gov/pubmed/20576948.
^ Twomey JA, Peltier GL, Zera RT (June 2007). "Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy". Arch Surg 142 (6): 546–51; discussion 551–3. doi:10.1001/archsurg.142.6.546. PMID 17576891.
^ Quizlet > Toxins and Antidotes
^ Tsurupa, G; Medved L (January 2001). "Identification and characterization of novel tPA- and plasminogen-binding sites within fibrin(ogen) alpha C-domains". Biochemistry (United States) 40 (3): 801–8. doi:10.1021/bi001789t. ISSN 0006-2960. PMID 11170397.
^ Ichinose, A; Takio K, Fujikawa K (July 1986). "Localization of the binding site of tissue-type plasminogen activator to fibrin". J. Clin. Invest. (UNITED STATES) 78 (1): 163–9. doi:10.1172/JCI112546. ISSN 0021-9738. PMC 329545. PMID 3088041. //www.ncbi.nlm.nih.gov/pmc/articles/PMC329545/.
^ Zhuo, M; Holtzman D M, Li Y, Osaka H, DeMaro J, Jacquin M, Bu G (January 2000). "Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation". J. Neurosci. (UNITED STATES) 20 (2): 542–9. PMID 10632583.
^ Orth, K; Madison E L, Gething M J, Sambrook J F, Herz J (August 1992). "Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 89 (16): 7422–6. doi:10.1073/pnas.89.16.7422. ISSN 0027-8424. PMC 49722. PMID 1502153. //www.ncbi.nlm.nih.gov/pmc/articles/PMC49722/.
^ Parmar, Parmjeet K; Coates Leigh C, Pearson John F, Hill Rena M, Birch Nigel P (September 2002). "Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cells". J. Neurochem. (England) 82 (6): 1406–15. doi:10.1046/j.1471-4159.2002.01100.x. ISSN 0022-3042. PMID 12354288.

External links

Tissue Plasminogen Activator from the American Heart Association
Widening the Window : Strategies to buy time in treating ischemic stroke - Scientific American Magazine (August 2005)
Study expands window for effective stroke treatment - explained on YouTube

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 止血の概要 overview of hemostasis
2. 血栓溶解異常による血栓性および出血性疾患 thrombotic and hemorrhagic disorders due to abnormal fibrinolysis
3. 急性虚血性脳卒中に対する再灌流療法 reperfusion therapy for acute ischemic stroke
4. 血管内皮機能および血栓溶解療法の基本的メカニズム vascular endothelial function and fundamental mechanisms of fibrinolysis thrombolysis
5. 線溶マーカーおよび心血管リスク fibrinolytic markers and cardiovascular risk

English Journal

Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

Komanapalli ES1, Sherchan P2, Rolland W 2nd2, Khatibi N1, Martin RD1, Applegate RL 2nd1, Tang J2, Zhang JH3,4,5,6.
Acta neurochirurgica. Supplement.Acta Neurochir Suppl.2016;121:311-5. doi: 10.1007/978-3-319-18497-5_54.
Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been sho
PMID 26463967

A novel mouse model of thromboembolic stroke.

Chen Y1, Zhu W1, Zhang W1, Libal N1, Murphy SJ1, Offner H2, Alkayed NJ3.
Journal of neuroscience methods.J Neurosci Methods.2015 Dec 30;256:203-11. doi: 10.1016/j.jneumeth.2015.09.013. Epub 2015 Sep 18.
BACKGROUND: We previously demonstrated that tissue plasminogen activator (tPA) reduces infarct size after mechanical middle cerebral artery occlusion (MCAO) in wild-type (WT) mice and transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). Clinically, tPA limits ischemic damage by dissolvin
PMID 26386284

Recombinant PAI-1 therapy restores myoendothelial junctions and erectile function in PAI-1-deficient mice.

Kavoussi PK1, Heberlein K2, Straub AC3, Lowe GJ1, Oliver JL1, Smith RP1, Steers WD1, Annex BH3, Isakson BE2,3, Lysiak JJ1.
Andrologia.Andrologia.2015 Dec;47(10):1147-52. doi: 10.1111/and.12395. Epub 2014 Dec 29.
Myoendothelial junctions are specialised projections of cell : cell contact through the internal elastic lamina between endothelial cells and vascular smooth muscle cells. These junctions allow for endothelial cells and vascular smooth muscle cells to make direct membrane apposition and are involv
PMID 25557984

Japanese Journal

分析装置STACIAを用いた凝固分子マーカー検査における検体保存温度・方法の影響

八戸雅孝,末石真千子,三上容子
臨床病理 : 日本臨床検査医学会誌 60(12), 1139-1144, 2012-12
NAID 40019559630

症例報告左房粘液腫による心原性脳塞栓症の1例

畑山さや香,緒方利安,大川将和
Brain and nerve : 神経研究の進歩 64(10), 1175-1179, 2012-10
NAID 40019457094

Observational Investigation of Thrombolysis With the Tissue-Type Plasminogen Activator Monteplase for Acute Pulmonary Embolism in Japan

NIWA Akihiro,NAKAMURA Mashio,HARADA Natsumi,MUSHA Takashi
Circulation journal : official journal of the Japanese Circulation Society 76(10), 2471-2480, 2012-09-25
… Background: In Japan, the safety and efficacy of thrombolytic therapy using tissue-type plasminogen activator for acute pulmonary embolism (PE) in the real world remain unclear. …
NAID 10030875222

Related Pictures

★リンクテーブル★

国試過去問	「110D023」「110F029」「109I079」「112D072」「110D028」「109I021」「107I035」
リンク元	「組織プラスミノゲンアクチベータ」「組織プラスミノーゲン活性化因子」「組織プラスミノーゲンアクチベーター」「組織プラスミノーゲンアクチベータ」「tPA」
拡張検索	「recombinant tissue plasminogen activator」
関連記事	「activator」「plasminogen activator」

「110D023」

Plasminogen activator, tissue
	; PDB rendering based on 1a5h.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1A5H, 1BDA, 1PK2, 1PML, 1RTF, 1TPG, 1TPK, 1TPM, 1TPN
Identifiers
Symbols	PLAT; T-PA; TPA
External IDs	OMIM: 173370 MGI: 97610 HomoloGene: 717 ChEMBL: 1873 GeneCards: PLAT Gene
EC number	3.4.21.68
Gene Ontology
Molecular function	• serine-type endopeptidase activity; • protein binding;
Cellular component	• extracellular region; • extracellular space; • cytoplasm; • cell surface; • secretory granule; • extracellular matrix; • apical part of cell; • synapse;
Biological process	• response to hypoxia; • cellular protein modification process; • proteolysis; • blood coagulation; • smooth muscle cell migration; • plasminogen activation; • synaptic transmission, glutamatergic; • fibrinolysis; • response to peptide hormone stimulus; • negative regulation of proteolysis; • platelet-derived growth factor receptor signaling pathway; • regulation of synaptic plasticity; • blood vessel morphogenesis; • response to glucocorticoid stimulus; • response to cAMP;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

63歳の男性。前胸部痛を主訴に来院した。1か月前から、1週間に1回程度の頻度で200m程度の歩行時に前胸部痛が出現するようになった。今朝から、軽労作で2分程度の発作を繰り返すようになったため心配になって受診した。高血圧症と糖尿病の既往があり治療中であった。身長 164cm、体重 80kg。体温 36.8℃。脈拍72/分、整。血圧 166/92mmHg。心音と呼吸音とに異常を認めない。血液所見：赤血球 472万、Hb 13.2g/dL、Ht 40%、白血球 7,800、血小板 16万。血液生化学所見：総蛋白 6.9g/dL、AST 32IU/L、ALT 34IU/L、LD 210IU/L(基準 176～353)、CK 122IU/L(基準 30～140)、尿素窒素 23mg/dL、クレアチニン 0.9mg/dL、空腹時血糖 130mg/dL、HbA1c 7.2%(基準4.6～6.2)、トリグリセリド 190mg/dL、HDLコレステロール 25mg/dL、LDLコレステロール 148mg/dL、Na 136mEq/L、K 3.8mEq/L、Cl 100mEq/L、トロポニンT陰性。胸部エックス線写真で異常を認めない。心電図を施行するため検査室に移動したところ、胸部症状が出現した。その時の心電図(別冊No. 2Ａ)を別に示す。直ちに硝酸薬の舌下投与を行い、2分程度で症状は改善した。改めて施行された心電図(別冊No. 2Ｂ)を別に示す。急性冠動脈症候群の診断で緊急入院となり、冠動脈造影を施行された。冠動脈造影像(別冊No. 2Ｃ、Ｄ)を別に示す。
この患者への対応として適切なのはどれか。

a　冠動脈バイパス術
b　経皮的心肺補助(PCPS)
c　心臓リハビリテーション
d　運動負荷心筋シンチグラフィ
e　t-PA(tissue plasminogen activator)の投与

[正答]

※国試ナビ4※　［110D022］←［国試_110］→［110D024］

「110F029」

　　[★]

次の文を読み、28、29の問いに答えよ。
72歳の男性。突然の背部痛と冷汗とを主訴に来院した。
現病歴：本日午後2時、庭仕事中に突然の背部痛と冷汗とを自覚した。背部痛は、痛み始めが最も強く、腰部へ移動した。症状が続くため受診した。
既往歴：53歳時に高血圧症を指摘され自宅近くの診療所に通院中である。
生活歴：夫婦2人暮らし。現在は無職。喫煙は70歳まで25本/日を50年間。飲酒は機会飲酒。
現症：意識は清明。身長 158cm、体重 60kg。脈拍 120/分、整。右上肢血圧 178/90mmHg、左上肢血圧 172/92mmHg。心音と呼吸音とに異常を認めない。
検査所見：尿所見：蛋白(－)、糖(－)。血液所見：赤血球 450万、Hb 13.8g/dL、Ht 42%、白血球 11,800(桿状核好中球 22%、分葉核好中球 40%、好酸球 2%、好塩基球 1%、単球 7%、リンパ球 28%)、血小板 18万。血液生化学所見：総蛋白 6.0g/dL、AST 52IU/L、ALT 55IU/L、LD 290IU/L(基準 176～353)、尿素窒素 32mg/dL、クレアチニン 0.9mg/dL、CK 98IU/L(基準 30～140)。胸部CT水平断像(別冊No. 5Ａ)、腹部CT水平断像(別冊No. 5Ｂ)及び胸腹部CT矢状断像(別冊No. 5Ｃ)を別に示す。

この時点の治療で適切なのはどれか。

a　降圧療法
b　腎血管形成術
c　冠動脈形成術
d　心臓リハビリテーション
e　t-PA(tissue plasminogen activator)の投与

[正答]

※国試ナビ4※　［110F028］←［国試_110］→［110F030］

「109I079」

　　[★]

58歳の男性。胸痛を主訴に来院した。1週前、プールで水泳中に締め付けられるような胸痛を初めて自覚した。痛みは数分で消失した。昨日の夕食後に同様の強い症状が出現し、約1時間で改善したためそのまま入眠した。今朝になって心配した家族に連れられて受診した。喫煙は20本/日を38年間。糖尿病にて食事指導と運動指導とを受けている。意識は清明。身長 160cm、体重 59kg。体温 36.3℃。脈拍 96/分、整。血圧 150/84mmHg。呼吸数16/分。SpO2 98%(room air)。眼瞼結膜に異常を認めない。頸静脈の怒張を認めない。心音と呼吸音とに異常を認めない。血液所見：赤血球 430万、Hb 14.0g/dL、Ht 36%、白血球 6,200、血小板 22万。血液生化学所見：心筋トロポニンT 陽性、CK 239IU/L(基準 30～140)、CK-MB 23IU/L(基準 20以下)。胸部エックス線写真で異常を認めない。心電図(別冊No. 31Ａ)と冠動脈造影像(別冊No. 31Ｂ、Ｃ)とを別に示す。
治療として適切なのはどれか。3つ選べ。

a　硝酸薬投与
b　冠動脈バイパス術
c　ヘパリンの持続静注
d　経皮的心肺補助(PCPS)の実施
e　t-PA(tissue plasminogen activator)の静脈内投与

[正答]

※国試ナビ4※　［109I078］←［国試_109］→［109I080］

「112D072」

　　[★]

43歳の男性。突発する強い頭痛のため妻に付き添われて来院した。10日前から毎日明け方に右眼の奥が痛くて目が覚めるようになった。痛みは1時間程度で治まっていたが、今朝は午前5時ごろから右眼の奥をえぐられるような激しい痛みだったので耐えられなくなり、午前6時30分に救急外来を受診した。昨夜は大量飲酒をして就寝したという。30歳台から高血圧症で降圧薬を服用中である。1年前にも同様の頭痛が1週間続いたことがあったという。喫煙は20本/日を22年間。意識は清明。体温 36.6℃。脈拍 84/分、整。血圧 152/94mmHg。呼吸数 16/分。瞳孔径は右 2.5mm、左 3.5mmで、対光反射は迅速である。右眼の結膜充血と流涙とを認める。発語に異常はなく、四肢の麻痺も認めない。腱反射は正常で、Babinski徴候は両側陰性である。頭部MRIとMRAに異常を認めない。
適切な治療はどれか。2つ選べ。

a　酸素投与
b　ヘパリン静注
c　トリプタン皮下注
d　グリセリン点滴静注
e　t-PA(tissue plasminogen activator)静注

[正答]

※国試ナビ4※　［112D071］←［国試_112］→［112D073］

「110D028」

　　[★]

78歳の男性。前胸部痛を主訴に来院した。胸痛は1時間前に朝食の準備をしていたところ突然生じ、前胸部から咽頭部、両頸部にかけての締め付けられる痛みで現在も持続している。高血圧症と脂質異常症で5年前から内服治療を継続している。意識は清明。身長 166cm、体重 72kg。体温 36.8℃。脈拍 40/分、整。血圧 120/60mmHg。呼吸数18/分。SpO2 99%(room air)。心電図(別冊No. 7Ａ)を別に示す。心電図検査の後から、突然の一過性の意識消失発作を繰り返すようになった。この時の心電図モニターの波形(別冊No. 7Ｂ)を別に示す。
直ちに投与すべき薬剤はどれか。