Dipyridamole enhances tissue plasminogen activator release by brain capillary endothelial cells

Kim, Jeong‐A; Tran, Nam; Zhou, Weilin; Fisher, Mark

doi:10.1016/j.thromres.2004.10.001

Cited by 11 publications

(6 citation statements)

References 16 publications

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“…Further, Kim et al . reported increases in brain capillary endothelial release of tissue plasminogen activator, when DP was added to the culture 17 . Although not significant, in our RMCAO we observed a reduction in injected clot size in DP‐treated animals, at the time of euthanasia, compared to nontreated animals.…”

Section: Dipyridamole Antithrombotic Mechanismscontrasting

confidence: 48%

Effect of dipyridamole during acute stroke: exploring antithrombosis and neuroprotective benefits

2010

Annals of the New York Academy of Sciences

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Currently, many stroke-prone individuals take antithrombotic drugs, which have known antiplatelet properties, to decrease stroke incidence. There is now evidence that this regimen could also reduce stroke severity through neuroprotective, nonplatelet mechanisms that include anti-inflammatory processes. Inflammation was found to play an important role in atherosclerosis/thrombosis development and acute stroke progression. In light of these findings, prevention strategies that target inflammatory mediators are under investigation. A common secondary stroke prevention therapeutic, dipyridamole, has shown promise for reducing stroke recurrence without increasing bleeding. In addition to its antiplatelet ability, dipyridamole has positive effects on vascular endothelium and inflammation. This review explores the effect of dipyridamole during acute stroke, revealing its potential use for improving poststroke clinical outcome.

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Section: Dipyridamole Antithrombotic Mechanismscontrasting

confidence: 48%

Effect of dipyridamole during acute stroke: exploring antithrombosis and neuroprotective benefits

2010

Annals of the New York Academy of Sciences

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“…Dipyridamole has been shown to enhance the release of t-PA from capillary endothelial cells [86]. Recently, a Kruppel-like factor 2 (KLF2) has been shown to be a transcriptional regulator of endothelial thrombotic function.…”

Section: Potential Targets For Pharmacological Enhancement Of Endogenmentioning

confidence: 99%

Enhanced spontaneous thrombolysis: A new therapeutic challenge

Kovács

Gorog²,

Yamamoto

2006

J Thromb Thrombolysis

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Spontaneous thrombolysis is an endogenous protective mechanism against lasting arterial thrombotic occlusion, which is implicated in the pathogenesis of myocardial infarction and acute coronary events. Novel therapies for coronary heart disease (CHD) targeting atherosclerosis and thrombosis, together with cardiovascular prevention programs targeting risk-factors and lifestyle provide evidence that CHD is preventable. Although reduced fibrinolytic activity is a recognized risk-factor for ischemic cardiovascular events, it has so far been neglected. Our knowledge of the fibrinolytic effect of drugs commonly used for CHD such as antiplatelet agents (aspirin, ticlopidine, clopidogrel), anti-diabetic biguanides (phenformin, metformin) or anti-hypertensive drugs is scanty and conflicting. This is mainly due to the lack of a global test of spontaneous thrombolysis, as opposed to fibrinolysis of plasma or whole blood, i.e. the assessment of various activators and inhibitors of the fibrinolytic system. A recently described technique allows the measurement of spontaneous thrombolysis, that is, lysis of an autologous platelet-rich thrombus in the absence of added plasminogen activators. Early results suggest that this test may have significant clinical potential both in identifying those at risk of fatal cardiac events and in finding new therapeutic avenues or lifestyles to improve spontaneous thrombolytic activity.

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“…The relationship between fibrinolysis and stroke has been further emphasized by work showing that genetically determined impairment of tPA release significantly increases the risk of lacunar stroke (Jannes et al, 2004), and that an important stroke prevention drug increases the release of brain endothelial tPA (Kim et al, 2005). Moreover, there is evidence that stroke risk is transiently increased after systemic infections (Paganini-Hill et al, 2003;Smeeth et al, 2004) and that this might be explained by impairment of fibrinolysis associated with these infections (Macko et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Brain Endothelial Hemostasis Regulation by Pericytes

Kim

Tran

et al. 2006

J Cereb Blood Flow Metab

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Pericytes are known to regulate brain capillary endothelial functions. The purpose of this study was to define the hemostatic regulatory role of human brain pericytes. We used blood-brain barrier models consisting of human pericytes grown on transwell membrane inserts and cocultured with human brain microvascular endothelial cells (HBEC), or pericytes grown in direct contact with HBEC. When grown in cocultures in which pericytes were physically separated from endothelial cells, pericytes induced significant changes in endothelial tissue plasminogen activator (tPA) messenger ribonucleic acid (mRNA) and protein: tPA mRNA level was decreased in pericyte cocultures (52%+/-25% of monocultures, P < 0.05) and tPA protein level was decreased (66%+/-23% of monocultures, P < 0.05). Pericyte effects on endothelial fibrinolysis were enhanced when the two cell types were cocultured in direct contact, with tPA protein reduced in cocultures compared with monocultures (25%+/-15% of monocultures, P < 0.05). Endotoxin (lipopolysaccharide (LPS)), used as a standardized stimulus to define brain-specific inflammation-induced change, amplified pericyte-induced enhanced release of the tPA inhibitor plasminogen activator inhibitor-1 (PAI-1); the latter was released by endothelial cells first cocultured with pericytes and then incubated with LPS in the absence of pericytes. Pericytes (in contrast to endothelial cells and astrocytes) were found to be the principal in vitro source of the serpin protease nexin-1 (PN-1), known to have primarily antithrombin effects. These in vitro findings suggest that pericytes negatively regulate brain endothelial cell fibrinolysis, while pericyte expression of PN-1 may provide endogenous anticoagulant activity.

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Dipyridamole enhances tissue plasminogen activator release by brain capillary endothelial cells

Cited by 11 publications

References 16 publications

Effect of dipyridamole during acute stroke: exploring antithrombosis and neuroprotective benefits

Effect of dipyridamole during acute stroke: exploring antithrombosis and neuroprotective benefits

Enhanced spontaneous thrombolysis: A new therapeutic challenge

Brain Endothelial Hemostasis Regulation by Pericytes

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