Synergistic Effect of Thrombin and CD40 Ligand on Endothelial Matrix Metalloproteinase-10 Expression and Microparticle Generation In Vitro and In Vivo

Lizarrondo, Sara Martínez de; Roncal, Carmen; Calvayrac, Olivier; Rodrı́guez, Cristina; Varo, Nerea; Purroy, Ana; Lorente, Leonardo; Rodríguez, José Antonio; Doeuvre, Loïc; Hervás-Stubbs, Sandra; Anglès-Cano, Eduardo; Páramo, José A.; Martínez-González, José; Orbe, Josune

doi:10.1161/atvbaha.112.248773

Cited by 56 publications

(52 citation statements)

References 42 publications

(44 reference statements)

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“…Previous clinical studies including our own have shown higher circulating levels of MMP-9 and TIMP-1 in septic patients than in controls [12]–[22], and higher levels of TIMP-1 [15], [19], [20], [23] at the time of severe sepsis diagnosis in non-surviving than in surviving patients. In addition, an association between circulating TIMP-1 and plasminogen activator inhibitor (PAI)-1 levels in septic patients at severe sepsis diagnosis has been reported [23].…”

Section: Introductionmentioning

confidence: 49%

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

et al. 2014

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ObjectiveHigher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and non-surviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions.MethodsMulticenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality.ResultsWe found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p<0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8.ConclusionsThe novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.

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Section: Introductionmentioning

confidence: 49%

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

et al. 2014

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“…In response to the generation of thrombin, local platelets release exosomal EVs that mediate paracrine signaling to endothelial cells [29]. In turn, the endothelial cells release EVs enriched with matrix metallopreinase-10, which exacerbate the pro-inflammatory vascular wall remodeling [30]. Acetylsalicylic acid (aspirin) treatment significantly reduces the release of exosomal EVs from platelets [29], perhaps contributing to its function in preventing thrombosis.…”

Section: Extracellular Vesicles As Mediators Of Cell-matrix Interactionsmentioning

confidence: 99%

Extracellular vesicles in cardiovascular homeostasis and disease

Hutcheson

Aikawa

2018

Current Opinion in Cardiology

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Purpose of review Extracellular vesicles (EVs) have emerged as one of the most important means through which cells interact with each other and the extracellular environment, but EV research remains challenging due to their small size and limited amount of material required for traditional molecular biology assays. The advent of new technologies and standards in the field, however, have led to increased mechanistic insight into EV function. Herein, the latest studies on the role of EVs in cardiovascular physiology and pathology are discussed. Recent findings EVs help control cardiovascular homeostasis and remodeling by mediating communication between cells and directing alterations in the extracellular matrix to respond to changes in the environment. The message carried from the parent cell to extracellular space can be intended for both local (within the same tissue) and distal (downstream of blood flow) targets. Pathological cargo loaded within EVs could further result in various diseases. On the other hand, new studies indicate that injection of EVs obtained from cultured cells into diseased tissues can promote restoration of normal tissue function. Summary EVs are an integral part of cell and tissue function, and harnessing the properties inherent to EVs may provide a therapeutic strategy to promote tissue regeneration.

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“…In other clinical circumstances, such as patients with acute coronary syndrome [58] , sepsis [59,60] , and brain trauma injury [61] , also circulating sCD154 levels have been associated with poor prognosis. Interestingly, a positive association between circulating levels of sCD154 and tissue factor (p < 0.001) and TNF-alpha (p < 0.001) in patients with severe MMCAI patients was reported for the first time in our study.…”

Section: Soluble Cd154mentioning

confidence: 99%

Section: Soluble Cd154mentioning

confidence: 99%

“…We found that the area under the curve to predict mortality at 30 days for serum sCD154 levels was of 0.80 (95% CI = 0.66-0.90; p < 0.001). In survival analysis was found a higher mortality at 30 days in patients with serum sCD154 levels higher than 1.41 ng/mmL than in patients with lower levels (Hazard ratio = 3.4; 95% CI = 1.58-7.39; p = 0.006).In other clinical circumstances, such as patients with acute coronary syndrome [58] , sepsis [59,60] , and brain trauma injury [61] , also circulating sCD154 levels have been associated with poor prognosis. Interestingly, a positive association between circulating levels of sCD154 and tissue factor (p < 0.001) and TNF-alpha (p < 0.001) in patients with severe MMCAI patients was reported for the first time in our study.…”

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confidence: 97%

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New prognostic biomarkers in patients with ischemic stroke

Lorente

2016

Mol Med Chem

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Ischemic stroke leads to disability and mortality and involved great consumption of resources. This review focuses on new prognostic biomarkers of mortality in patients with ischemic stroke in relation to the inflammation, coagulation, and oxidation. Blood concentration of tissue inhibitor of matrix metalloproteinases (TIMP)-1, soluble CD154 (sCD154), and malondialdehyde (MDA) in ischemic stroke patients have been recently found to be associated with mortality. Matrix metalloproteinases (MMPs) are zinc-containing endoproteinases involved in neuroinflammation during cerebral ischemia and TIMP-1 is the inhibitor of some of them. sCD154 is a member of the tumor necrosis factor (TNF) family that is released into circulation from different cells and when binding to their cell surface receptor showed proinflamatory and procoagulant properties. MDA is a low molecular weight aldehyde and appears due to the attacks from free radical to phospholipids of cellular membrane. The determination of circulating levels of those biomarkers could help in the prognostic classification of the patients. In addition, the modulation of those pathways could open new research lines for the treatment of ischemic stroke patients.Keywords: Ischemic stroke; biomarkers; TIMP-1; sCD154; malondialdehyde To cite this article: Leonardo Lorente. New prognostic biomarkers in patients with ischemic stroke. Mol Med Chem 2015; 1: e972. doi: 10.14800/mmc.972. IntroductionIschemic stroke leads to disability and mortality and involved great consumption of resources [1] . This review focuses on new prognostic biomarkers of mortality in patients with ischemic stroke in relation to the inflammation, coagulation, and oxidation. Tissue inhibitor of matrix metalloproteinases-1Matrix metalloproteinases (MMPs) are zinc-containing endoproteinases, which could be classified according to the substrate specificity in gelatinases (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8 and MMP-13), stromelysins (MMP-3, MMP-10, MMP-11), matrilysins (MMP-7), elastases (MMP-12) and membrane-type (MMP-14, MMP-15, MMP-16 and MMP-17). MMPs are involved in the processes of degradation and remodelling of the extracellular matrix (ECM). MMP activity is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs are involved in physiological functions such as morphogenesis, tissue remodelling, menstrual cycle, and angiogenesis; and also in different diseases as tumour, arthritis, sepsis, and atherosclerosis [2] .Cerebral ischemia activate an inflammatory response and are released different cytotoxic agents, such as MMPs, which could favorate disruption of the blood-brain barrier (BBB) and cell damage [3] .There have been found higher circulating MMP-9 levels in ischemic stroke patients than in controls [4][5][6][7][8] , and also in patients with ischemic stroke and worse functional outcome compared with patients with better outcome [4][5][6][7][8][9][10][11][12] . Also, higher circulating levels of MMP-10 in ischemic stroke patients than in controls there have been f...

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Synergistic Effect of Thrombin and CD40 Ligand on Endothelial Matrix Metalloproteinase-10 Expression and Microparticle Generation In Vitro and In Vivo

Cited by 56 publications

References 42 publications

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

Association of Sepsis-Related Mortality with Early Increase of TIMP-1/MMP-9 Ratio

Extracellular vesicles in cardiovascular homeostasis and disease

New prognostic biomarkers in patients with ischemic stroke

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