Extracellular Matrix Metalloproteinase Inducer Regulates Matrix Metalloproteinase Activity in Cardiovascular Cells

Schmidt, Roland; Bültmann, Andreas; Ungerer, Martin; Joghetaei, Nader; Bülbül, Özgür; Thieme, Sven F.; Chavakis, Triantafyllos; Toole, Bryan P.; Gawaz, Meinrad; Schömig, Albert; May, Andreas E.

doi:10.1161/circulationaha.105.568162

Cited by 155 publications

(169 citation statements)

References 28 publications

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“…[19][20][21][22][23][24] Recent studies provide evidence that CyPA is also present in the cytoplasm of platelets and can be released from granules upon platelet activation to bind to endothelial cells, monocytes, and macrophages via the CyPA receptor EMMPRIN (CD147), thereby inducing a signaling cascade into the target cell (eg, degranulation or expression of matrix metalloproteinases. 19,23,[25][26][27][28] The function of intracellular CyPA in platelets has not yet been explored.In the present study, we show for the first time that CyPA deficiency leads to multiple platelet activation defects caused by strongly reduced Ca 2ϩ mobilization from intracellular stores and Ca 2ϩ entry from the extracellular space. Our results identify CyPA as a powerful Ca 2ϩ regulator in platelets.…”

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confidence: 99%

Intracellular cyclophilin A is an important Ca2+ regulator in platelets and critically involved in arterial thrombus formation

Elvers

Herrmann

Seizer

et al. 2012

Blood

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Platelet adhesion and aggregation play a critical role in primary hemostasis. Uncontrolled platelet activation leads to pathologic thrombus formation and organ failure. The decisive central step for different processes of platelet activation is the increase in cytosolic Ca 2؉ activity ([Ca 2؉ ] i ). Activation-dependent depletion of intracellular Ca 2؉ stores triggers Ca 2؉ entry from the extracellular space. Stromal interaction molecule 1 (STIM1) has been identified as a Ca 2؉ sensor that regulates store-operated Ca 2؉ entry through activation of the pore-forming subunit Orai1, the major store-operated Ca 2؉ entry channel in platelets. In the present study, we show for the first time that the chaperone protein cyclophilin A (CyPA) acts as a Ca 2؉ modulator in platelets. CyPA deficiency strongly blunted activation-induced Ca 2؉ mobilization from intracellular stores and Ca 2؉ influx from the extracellular compartment and thus impaired platelet activation substantially. Furthermore, the phosphorylation of the Ca 2؉ sensor STIM1 was abrogated upon CyPA deficiency, as shown by immunoprecipitation studies. In a mouse model of arterial thrombosis, CyPAdeficient mice were protected against arterial thrombosis, whereas bleeding time was not affected. The results of the present study identified CyPA as an important Ca 2؉ regulator in platelets, a critical mechanism for arterial thrombosis. IntroductionPlatelet adhesion and aggregation are essential for hemostasis at sites of vascular injury to avoid excessive blood loss. 1,2 In contrast, uncontrolled platelet activation can induce acute vessel occlusion, leading to myocardial infarction or stroke at areas of atherosclerotic plaque rupture. 3,4 Platelet activation and thrombus formation is a multistage process that involves different signaling pathways to trigger platelet shape change, integrin activation, and degranulation. 4,5 The signaling pathways converge in the activation of phospholipase C (PLC), leading to the formation of inositol 1,4,5-triphosphate (IP 3 ) and diacylglycerol. 6 IP 3 is then able to bind to its receptor at the endoplasmic reticulum (ER) and mediates Ca 2ϩ efflux from the intracellular stores into the cytoplasm. 6,7 Compromised PLC activation impairs Ca 2ϩ mobilization, which is followed by defective thrombus formation under flow conditions. 8,9 Stromal interaction molecule 1 (STIM1) is a type I singletransmembrane protein with an N-terminal EF hand domain (helix-loop-helix structural domain) that binds Ca 2ϩ in the lumen of the ER. STIM1 binding to Ca 2ϩ is interrupted upon store release and induces redistribution of STIM1 to the plasma membrane to open store-operated Ca 2ϩ (SOC) channels, thereby stimulating store-operated Ca 2ϩ entry (SOCE). 10,11 Orai1 was identified as the major SOCE channel in platelets known to be regulated by the Ca 2ϩ sensor STIM1. 12,13 Immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPIs) that interconvert between the cis and trans positions of target proteins. 14,15 According to their sensitivity t...

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Intracellular cyclophilin A is an important Ca2+ regulator in platelets and critically involved in arterial thrombus formation

Elvers

Herrmann

Seizer

et al. 2012

Blood

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“…Extracellular matrix metalloproteinase inducer (EMM-PRIN) triggers the synthesis of MMP-9 in a paracrine or autocrine manner (Zhou et al, 2005;Schmidt et al, 2006). Increasing evidence shows that in response to certain proatherogenic stimuli such as oxLDL, EMMPRIN is upregulated strongly in atherosclerosis-related cells, including macrophages and coronary smooth muscle cells (Major et al, 2002;Haug et al, 2004;Schmidt et al, 2006).…”

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confidence: 99%

“…Increasing evidence shows that in response to certain proatherogenic stimuli such as oxLDL, EMMPRIN is upregulated strongly in atherosclerosis-related cells, including macrophages and coronary smooth muscle cells (Major et al, 2002;Haug et al, 2004;Schmidt et al, 2006). It also increases in activated platelets and mediated NF-jB activation by inducing the production of MMP-9, IL-6, and TNF-a (Schmidt et al, 2008).…”

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Suppression of oxLDL‐Induced MMP‐9 and EMMPRIN Expression by Berberine via Inhibition of NF‐κB Activation in Human THP‐1 Macrophages

Huang

Shao

Wang

et al. 2011

The Anatomical Record

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Upregulation of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) by macrophages leads to atherosclerotic plaque rupture by degradation of the extracellular matrix. NF-jB activation regulates many key inflammatory genes linked to atherosclerosis. In the present study, the function of berberine, a natural extract from Rhizoma coptidis, on MMP-9 and EMMPRIN expression, the role of NF-jB activation in oxLDL-stimulated macrophages, and the possible mechanism in which NF-jB activation is involved were investigated. Berberine inhibited the expression of MMP-9 and EMMPRIN at both mRNA and protein levels. The phosphorylation of IjB-a and nuclear translocation of p65 protein were reduced by berberine, suggesting that NF-jB activation was inhibited by berberine in oxLDL-stimulated macrophages. Overall, berberine suppressed the expression of MMP-9 and EMMPRIN by at least reducing partly the activity of NF-jB in oxLDL-induced macrophages. Anat Rec, 295:78-86, 2012. V V C 2011 Wiley Periodicals, Inc.

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“…Максимально повышенное содержание гликоза-миногликанов в первые трое суток при остром инфар-кте миокарда свидетельствует о деструктивных про-цессах во внеклеточном матриксе миокарда [6]. На 10-12 сутки отмечается высокое содержание фибронектина, пептидно-связанного оксипролина, снижение уровня гликозаминогликанов.…”

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“…Как известно, после гибели кардиомиоцитов при ИМ репарация осуществляется за счет соединитель-ной ткани, в состав которой входят клеточные эле-менты (фибробласты) и внеклеточный матрикс [6]. Регуляция синтеза и распада белков внеклеточного мактрикса осуществляется системой матриксных металлопротеиназ и ее тканевых ингибиторов [1,7].…”

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The Values of Matrix Metalloprotease-9 and Tissue Metalloprotease Inhibitor-1 in Acute Myocardial Infarction With Aneurysm Formation

Говорин¹,

Рацина²,

Sokolova³

et al. 2014

Russ J Cardiol

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Цель. Изучить в крови показатели системы ММР-9 и TIMP-1 в динамике у больных с острым трансмуральным передним инфарктом миокарда, ослож-ненным аневризмой. Материал и методы. В исследование включено 46 больных острым трансму-ральным передним инфарктом миокарда, у которых показатели MMP-9 и TIMP-1 были изучены в динамике. Результаты. В 1-3 сутки у больных ИМ без аневризмы отмечалось значитель-ное повышение ММР-9 до 229,8 нг/мл, к 10-12-му дню -снижение и вновь нарастание до 237,3 нг/мл к 18-22 дню. У больных ИМ с аневризмой в 1-3 и 10-12 сутки содержание ММР-9 увеличивалось незначительно, и лишь к 18-22 дню отмечалось более существенное повышение показателей до 159,2 нг/мл. Содержание TIMP-1 у больных ИМ без аневризмы постепенно нарастало от 1-3 дня (698,9 нг/мл) к 18-22 дню (942,3 нг/мл). У больных ИМ с аневризмой в 1-3 и 10-12 сутки отмечались максимальные показатели TIMP-1, которые постепенно уменьшались к 18-22 дню. Заключение. Выявленные изменения показателей ММР-9 и TIMP-1, возможно, указывают на отсрочку процессов репарации у больных ИМ с аневризмой. Российский кардиологический журнал 2014, 7 (111): 87-90Ключевые слова: острый трансмуральный передний ИМ, аневризма, внекле-точный матрикс, ММР-9, TIMP-1. THE VALUES OF MATRIX METALLOPROTEASE-9 AND TISSUE METALLOPROTEASE INHIBITOR-1 IN ACUTE MYOCARDIAL INFARCTION WITH ANEURYSM FORMATIONGovorin A. V. Aim. To study the blood levels of MMP-9 and TIMP-1 in dynamic in patients with acute transmural anterior myocardial infarction complicated by aneurysm. Material and methods. 46 patients with acute transmural anterior myocardial infarction were included into the study. The blood levels of MMP-9 and TIMP-1 were studied.Results. In 1-3 days the patients with myocardial infarction without aneurysm had a significant increase in MMP-9 up to 229,8 ng/ml, then to 10-12th days a decrease and then increase again up to 237,3 ng/ml by 18-22th days. In patients with myocardial infarction complicated by an aneurysm at 1-3rd and 10-12th days the level of MMP-9 increased slightly, and only at 18-22th days we observed significant increases of MMP-9 up to 159,2 ng/ml. In patients with myocardial infarction without aneurysm the level of TIMP-1 gradually grew up from 1-3rd days (698,9 ng/ml) to 18-22th days (942,3 ng/ml). In patients with myocardial infarction complicated by an aneurysm at 1-3rd and 10-12th days we observed maximum values of TIMP-1, gradually decreased to 18-22th days. Conclusion. The changes found in MMP-9 and TIMP-1 levels might indicate a delay of reparation processes in patients with myocardial infarction complicated by an aneurysm. Russ J Cardiol 2014, 7 (111): 87-90

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Extracellular Matrix Metalloproteinase Inducer Regulates Matrix Metalloproteinase Activity in Cardiovascular Cells

Cited by 155 publications

References 28 publications

Intracellular cyclophilin A is an important Ca2+ regulator in platelets and critically involved in arterial thrombus formation

Intracellular cyclophilin A is an important Ca2+ regulator in platelets and critically involved in arterial thrombus formation

Suppression of oxLDL‐Induced MMP‐9 and EMMPRIN Expression by Berberine via Inhibition of NF‐κB Activation in Human THP‐1 Macrophages

The Values of Matrix Metalloprotease-9 and Tissue Metalloprotease Inhibitor-1 in Acute Myocardial Infarction With Aneurysm Formation

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