&amp;#945;2-Antiplasmin: Potential Therapeutic Roles in Fibrin Survival and Removal

Lee, Kyung N.; Jackson, Kenneth W.; Christiansen, Victoria J.; Chung, Keun Hee; McKee, Patrick A.

doi:10.2174/1568016043356228

Cited by 23 publications

(22 citation statements)

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“…. [15][16][17][18]. The crystal structure of FAP has been elucidated, and comparison with the crystal structure of DPP4 points to a lower anchoring of substrates by Glu 203 -Glu 204 due to shielding effects of surrounding hydrophobic residues and lack of Asp 663 .…”

Section: Dpp4 Gene Familymentioning

confidence: 99%

“…Recently, the role FAP in cartilage degradation could be elucidated in FAP-knock-out of tumour necrosis factor (TNF)-a transgenic mice [FAP (-/-) human TNF transgenic (hTNFtg) mice], as these animals revealed less cartilage degradation, but similar inflammation and bone erosion compared to wild-type hTNFtg mice [29]. Cleavage of a 2 -anti-plasmin by soluble serum-FAP yields a more active form, thereby promoting fibrosis and scar formation [17,18]. Thus, FAP has an opposite physiological role compared to DPP4 that enhances fibrinolysis and scar resolution by activation of plasmin from plasminogen via a quintary complex of ADA, plasminogen 2, DPP4, urinary plasminogen activator (uPA/tPA) and plasminogen-receptor (Plg-R) [7].…”

Section: Dpp4 Gene Familymentioning

confidence: 99%

“…In addition, expression of FAP has been investigated in several types of cancers as potential biomarkers for epithelial colon, gastric, intestinal, oesophageal, undifferentiated thyroid, lung, breast, ovarian and cervical cancers, meningioma, glioma and cutaneous melanoma, as well as aggressive fibromatosus [7,12,15,17]. In cancers and capillaries where DPP4 and FAP co-localize, they form a heteromeric complex with both enzymes still maintaining their activities.…”

Section: Role Of Dash Proteins In Diseasesmentioning

confidence: 99%

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Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

101

107

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SummaryDipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins. Apart from DPP4, DASH proteins include fibroblast activation protein alpha (FAP), DPP8, DPP9, DPP4-like protein 1 (DPL1, DPP6, DPPX L, DPPX S), DPP4-like protein 2 (DPL2, DPP10) from the DPP4-gene family S9b and structurally unrelated enzyme DPP2, displaying DPP4-like activity. In contrast, DPP6 and DPP10 lack enzymatic DPP4-like activity. These DASH proteins play important roles in the immune system involving quiescence (DPP2), proliferation (DPP8/DPP9), antigen-presenting (DPP9), costimulation (DPP4), T cell activation (DPP4), signal transduction (DPP4, DPP8 and DPP9), differentiation (DPP4, DPP8) and tissue remodelling (DPP4, FAP). Thus, they are involved in many pathophysiological processes and have therefore been proposed for potential biomarkers or even drug targets in various cancers (DPP4 and FAP) and inflammatory diseases (DPP4, DPP8/DPP9). However, they also pose the challenge of drug selectivity concerning other DASH members for better efficacy and/or avoidance of unwanted side effects. Therefore, this review unravels the complex roles of DASH proteins in immunology.Keywords: antigen presentation/processing, CD26, co-stimulation, DPP4 activity and/or structure homologue proteins (DASH), signal transductionThe dipeptidyl peptidase (DPP)4 family of DPP4 activity and/or structure homologue (DASH) proteins Within the last two decades a number of enzymes have been discovered to also display DPP4-like activity or are structural homologues to DPP4. These enzymes/proteins are referred to as DPP4 activity and/or structure homologue (DASH) proteins, and can be grouped into the DPP4 gene family and non-related DPP4-like enzymes. Except for DPL1 and DPL2, all members display DPP4-like activity with neutral to basic pH optima and similar inhibition profiles [6,7]. DPP4 (CD26). DPP4 (CD26) is the best-known DASH protein and has been described in detail elsewhere [7][8][9].

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Section: Dpp4 Gene Familymentioning

confidence: 99%

Section: Dpp4 Gene Familymentioning

confidence: 99%

Section: Role Of Dash Proteins In Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

101

107

View full text Add to dashboard Cite

show abstract

“…It belongs to serpin family [92] and has hepatic origin. It is the main biological plasmin inhibitor which has about 90% of antiplasmin activity [93]. α 2-AP is known to be connected with plasmin which circulates in blood with the formation of inactive plasmin-α 2-antiplasmin complex [94][95][96].…”

Section: Partmentioning

confidence: 99%

The Dynamics of the Hemostatic Parameters in Physiological Pregnancy and After Delivery

Моmot¹

2016

HBTD

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Nowadays hematologists and obstetrician-gynecologists have little data about the peculiarities of hemostatic parameters and the maintenance of hemostatic balance at different stages of physiological pregnancy. However, it is necessary to know the norms for the determination of pathologic deviations in the system and medical decision making. The article presents the dynamics of 50 hemostatic parameters in women in pregravid period, at different stages of physiological pregnancy, and 2-3 days after vaginal delivery studied in 301 Caucasian (white) women. The parameters that characterize different components of hemostatic system were taken into account-vascular-platelet, coagulant, anticoagulant, and Fibrinolytic. Thrombin generation test was used as an integrated method to study hemocoagulation.According to the obtained results, some parameters were identified. These parameters could be an objective prerequisite for the prescription and monitoring the effects of antiaggregants and low molecular heparins during pregnancy with the aim of thromboprophylaxis. It is suggested that hyperproduction of Tissue Factor (TF) and thrombin (in relation to reference ranges) should play a possible role in initiation not only intravascular blood coagulation but also the end of pregnancy. It might be of importance in understanding the causes of preterm delivery. The described mechanism, preventing thrombus formation in late pregnancy, is associated with the enhancement of fibrinolytic reactions in blood circulation. This mechanism can lead to the degradation of soluble fibrin polymer (with the formation of D-dimers) before its conversion into gel or fibrin clot (fibrin insolubile). The obtained data could be useful in future to identify pregnant women at risk dealing with thrombosis, bleeding and obstetrics complications during pregnancy and delivery.Keywords: Blood coagulation markers; Coagulation factors; Fibrinolysis; Hemostatic system; Physiological anticoagulants; Pregnancy; Thrombin generation Citation: Моmot AP, Semenova NA, Belozerov DE, Trukhina DA, Kudinova IY (2016) interest since these data can be useful for the differential diagnostics of bleeding causes, as well as for the identification of patients needed in thromboprophylaxis.Moreover, simultaneous identification of a lot of parameters, characterizing coagulation, anticoagulant and fibrinolytic activity of blood could allow obtaining the important information about dynamically changing hemostatic balance during pregnancy, which is normally accompanied by neither bleedings nor thromboses. The study of these parameters is expected to explain the causes of 3-4 fold increase in D-dimers level in late physiological pregnancy, to select objective factors for initiation and cessation of heparinprophylaxis and to solve other problems associated with pregnancy complications.The aim of this study is to determine the allowed values and the dynamics of changes of a wide range of hemostatic parameters at different stages of physiological pregnancy and the first few day...

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“…Этот предста-витель семейства серпинов [21] является основным биоло-гическим ингибитором плазмина, и на его долю приходится около 90% антиплазминовой активности [40]. В частности, α 2 -АP связывает свободно циркулирующий в крови плазмин с образованием неактивного комплекса «плазмин -α 2 -АP» [23,44,46].…”

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Role of Blood Fibrinolytic Activity in Preventing Thrombosis in Normal Pregnancy

2016

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Белозёров Дмитрий Евгеньевич -врач клинической лабораторной диагностики лаборатории патологии гемостаза КГБУЗ «Краевая клиническая больница ». 656045, г. Барнаул, ул. Ляпидевского, д. 1. E-mail: dmitrbelozerov@yandex.ru Елыкомов Валерий Анатольевич -д. м. н., доцент, главный врач КГБУЗ «Краевая клиническая больница»; заведующий кафедрой терапии и общей врачебной практики факультета повышения квалификации и профессиональной переподготовки специалистов ГБОУ ВПО АГМУ Минздрава России. 656045, г. Барнаул, ул. Ляпидевского, д. 1. E-mail: hospital.akkb@mail Цель обзора: анализ современных представлений об участии фибринолитической системы крови в предотвращении тромбозов в позд-ние сроки беременности. Основные положения. Физиологическая беременность сопровождается повышением коагуляционной активности крови. Это связано с действием тканевого фактора и генерацией тромбина, о чем обычно свидетельствует рост уровня D-димеров в плазме крови. Однако остается неясной причина увеличения концентрации D-димеров в поздние сроки беременности, протекающей без какой-либо пато-логии. В обзоре представлен анализ динамики уровней плазминогена и основных регуляторов фибринолиза. Показано, что в период, предшествующий родам, возникает подавление пристеночных интраваскулярных фибринолитических реакций. В то же время систем-ный (в общей циркуляции) фибринолиз активирован. Заключение. Выдвинута гипотеза: в поздние сроки беременности концентрация D-димеров в плазме крови повышена вследствие лизи-са растворимого фибрина, не достигшего состояния фибринового сгустка. Ключевые слова: физиологическая беременность, генерация тромбина, фибрин, фибринолиз, D-димеры. С остояние беременности связано с естественной пере-стройкой работы органов и систем, сопровожда-ющейся системными изменениями гемостатическо-го и фибринолитического потенциалов крови, протром-богенными эффектами эндотелия кровеносных сосудов, а также снижением антикоагулянтой защиты [3,19]. Эти изменения приводят к нарастанию тромбогенности крови, достигающей максимума в поздние сроки физиологиче-ской беременности, что объясняется необходимостью уменьшить кровопотерю в родах [2,9,15,32,50]. Об активации свертывания крови в период вынашивания ребенка свидетельствует увеличение содержания в плаз-ме крови продуктов лизиса фибрина, обладающих анти-генами D-димеров, что связано с повышенным образова- To analyze current insights into the role of blood fibrinolytic activity in preventing thrombosis in the later stages of pregnancy. Key Points: Normal pregnancy is associated with increased blood coagulation. This is related to tissue-factor activity and the production of thrombin, which is usually seen in increased plasma D-dimers levels. However, the cause of this increase in D-dimers levels in the later stages of normal pregnancy remains unknown. This review includes an analysis of changes in the levels of plasminogen and key regulators of fibrinolysis. The authors show that intravascular fibrinolytic activity near the vessel wall is inhibited before delivery, while systemic fibrinolysis ...

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α2-Antiplasmin: Potential Therapeutic Roles in Fibrin Survival and Removal

Cited by 23 publications

References 0 publications

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

The Dynamics of the Hemostatic Parameters in Physiological Pregnancy and After Delivery

Role of Blood Fibrinolytic Activity in Preventing Thrombosis in Normal Pregnancy

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