A broad-spectrum matrix metalloproteinase inhibitor prevents hemorrhagic complications induced by tissue plasminogen activator in mice

Neuroscience ◽  
2012 ◽  
Vol 205 ◽  
pp. 39-48 ◽  
Author(s):  
K. Mishiro ◽  
M. Ishiguro ◽  
Y. Suzuki ◽  
K. Tsuruma ◽  
M. Shimazawa ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Broad Spectrum ◽  
Matrix Metalloproteinase Inhibitor ◽  
Metalloproteinase Inhibitor ◽  
Hemorrhagic Complications ◽  
Tissue Plasminogen

Blood markers of fibrinolysis system and vascular wall state in neonates born to mothers with preeclampsia

2021 ◽  
Author(s):  
И.Г. Попова ◽  
С.Б. Назаров ◽  
О.Г. Ситникова ◽  
Г.Н. Кузьменко ◽  
М.М. Клычева ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Venous Blood ◽  
Vascular Wall ◽  
Endothelial Damage ◽  
Control Group ◽  
Blood Levels ◽  
Hemorrhagic Complications ◽  
Tissue Plasminogen ◽  
Pai 1

Введение. Новорожденные, родившиеся у матерей с патологией во время беременности, составляют группу высокого риска тромботических и геморрагических осложнений, которые повышаются при наличии у новорожденных перинатальной патологии. Цель исследования: оценить показатели, характеризующие состояние системы фибринолиза и сосудистой стенки в крови новорожденных, родившихся у матерей с преэклампсией (ПЭ), для прогнозирования риска тромботических и геморрагических осложнений у таких детей. Материалы и методы. Обследовано 60 новорожденных, родившихся у матерей с ПЭ. Контрольную группу составили 30 новорожденных от матерей без ПЭ. Исследовали венозную кровь, взятую у новорожденных на 3–5-е сутки жизни. В крови определяли уровень тканевого активатора плазминогена (t-РА), ингибитора тканевого активатора плазминогена (PAI-1) и тромбомодулина. Результаты. Выявлено, что у новорожденных от матерей с ПЭ на 3–5-е сутки жизни отмечаются признаки повреждения эндотелия и повышение фибринолитической активности крови, на что указывает повышение содержания t-РА, PAI-1 и тромбомодулина в крови. Заключение. Полученные данные свидетельствуют о риске развития геморрагических осложнений у таких детей. Background. Neonates born to mothers with pathology during pregnancy are at high risk of thrombotic and hemorrhagic complications that are increased if neonates have perinatal pathology. Objectives: to assess blood parameters characterizing fibrinolysis and vascular wall of neonates born to mothers with preeclampsia (РЕ), to predict the risk of hemorrhagic complications in these children. Patients/Methods. 60 neonates born to mothers with РЕ were examined. The control group consisted of 30 neonates born to mothers without РЕ. We studied levels of tissue plasminogen activator (t-PA), inhibitor of tissue plasminogen activator (PAI-1) and thrombomodulin (TM) in venous blood taken from neonates on the 3–5th days of life. Results. In neonates born to mothers with PE we revealed on the 3–5th days of life increased blood levels of t-PA, PAI-1 and TM that characterized endothelial damage and increased blood fibrinolytic activity. Conclusions. The data obtained indicate the risk of hemorrhagic complications development in these children.

scholarly journals Successful ovulation in plasminogen-deficient mice treated with the broad-spectrum matrix metalloproteinase inhibitor galardin

2006 ◽  
Vol 295 (2) ◽  
pp. 615-622 ◽  
Author(s):  
Kui Liu ◽  
Patrik Wahlberg ◽  
Göran Leonardsson ◽  
Anna-Carin Hägglund ◽  
Annelii Ny ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Broad Spectrum ◽  
Matrix Metalloproteinase Inhibitor ◽  
Metalloproteinase Inhibitor ◽  
Deficient Mice

scholarly journals Reduction of Tissue Plasminogen Activator-Induced Matrix Metalloproteinase-9 by Simvastatin in Astrocytes

Stroke ◽  
2006 ◽  
Vol 37 (7) ◽  
pp. 1910-1912 ◽  
Author(s):  
Sophia Wang ◽  
Sun-Ryung Lee ◽  
Shu-Zhen Guo ◽  
Woo Jean Kim ◽  
Joan Montaner ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Matrix Metalloproteinase 9 ◽  
Tissue Plasminogen ◽  
Metalloproteinase 9

Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2610-2616 ◽  
Author(s):  
Bing-Qiao Zhao ◽  
Yasuhiko Ikeda ◽  
Hayato Ihara ◽  
Tetsumei Urano ◽  
WenYing Fan ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Cerebral Hemorrhage ◽  
Essential Role ◽  
Border Zone ◽  
Microglial Cells ◽  
Proteolytic Activation ◽  
Heparin Administration ◽  
Tissue Plasminogen

Abstract Cerebral hemorrhage associated with antithrombotic and thrombolytic therapy in acute stroke continues to present a major clinical problem. Rupture of the cerebral microvasculature involves the degradation and remodeling of extracellular matrix. Here we demonstrated that the delayed administration of heparin 3 hours after photothrombotic middle cerebral artery occlusion (MCAO) caused cerebral hemorrhage in wild-type (WT) mice but not in tissue plasminogen activator (tPA)–deficient knockout (KO) mice. Heparin administration increased tPA activity and its mRNA expression at 6 and 12 hours after MCAO in the ischemic hemispheres of WT mice. The expression of tPA was enhanced in microglial cells in the ischemic border zone. We also observed an exacerbation of matrix metalloproteinase (MMP) 9 expression at the mRNA level and its conversion to an active form after heparin administration in the ischemic hemisphere in WT mice but not in tPA KO mice. The increased MMP 9 expression was localized in microglial cells and endothelial cells. These findings suggest that endogenous tPA, through the enhancement of MMP 9 expression and proteolytic activation, plays an essential role in the pathogenesis of heparin-produced cerebral hemorrhage. Targeting tPA, MMP 9, or both may provide a new approach for preventing cerebral hemorrhage associated with antithrombotic therapy for stroke in humans.

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