Activated protein C and ischemic stroke

Griffin, John H.; Fernández, José A.; Liu, Dong; Cheng, Tong; Guo, Hao; Zloković, Berislav V.

doi:10.1097/01.ccm.0000126127.87484.2b

Cited by 45 publications

(28 citation statements)

References 52 publications

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“…The most striking effects of APC were visible on genes involved in the Bcl-2 family, which was also revealed in brain endothelial cells. 24 A study by Pirat et al also revealed an antiapoptotic effect of human APC after 20 minutes of ischemia and 2 hours of reperfusion, but an antiinflammatory effect on C-reactive protein or TNF-␣ levels was not visible possibly because of the short ischemic period used. 17 Direct effects of APC on neutrophil migration have been demonstrated in experimental models under conditions of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Activated Protein C Protects Against Myocardial Ischemia/ Reperfusion Injury via Inhibition of Apoptosis and Inflammation

Loubele

Spek

Leenders

et al. 2009

ATVB

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Objective-In spite of major advances in reperfusion therapy for patients presenting with acute coronary syndrome, long-term morbidity is still substantial. A limitation of initial treatment of myocardial ischemia is the lack of prevention of ischemia/reperfusion (I/R) injury. Activated protein C (APC), a crucial mediator in the coagulation process, plays a prominent role in the crosstalk between coagulation and inflammation and provides cytoprotective effects via inhibition of apoptosis and inflammation in several human and animal studies. Methods and Results-APC was administered in an animal model for myocardial I/R. APC largely inhibited early myocardial I/R injury after varying reperfusion times, an effect that was absent on administration of heparin, a nonspecific anticoagulant agent. The protective effects of APC were absent in case of absence or blockade of protease activated receptor-1 (PAR-1), indicating a critical role for PAR-1 in this process. Furthermore, we showed a strong antiapoptotic effect of APC in the early phase of reperfusion combined with an antiinflammatory effect at an early stage (IL-6), as well as at a later stage (leukocyte infiltration). Conclusions-APC

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Section: Discussionmentioning

confidence: 99%

Activated Protein C Protects Against Myocardial Ischemia/ Reperfusion Injury via Inhibition of Apoptosis and Inflammation

Loubele

Spek

Leenders

et al. 2009

ATVB

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“…103 The prospective epidemiologic Atherosclerosis Risk in Communities (ARIC) study reported that plasma protein C appeared protective against ischemic stroke (OR ϭ 0.65 [0.4-1.0]). 104 In murine models of focal cerebral ischemia, APC provided remarkable anti-inflammatory and neuroprotective effects.…”

Section: Apc In Ischemic Strokementioning

confidence: 99%

The cytoprotective protein C pathway

Mosnier

Zloković

Griffin

2006

Blood

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696

824

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“…[91][92][93] Indeed, in a murine model of focal cerebral ischemia, administration of aPC reduced cerebrovascular and brain damage by inhibiting infiltration of leukocytes in For personal use only. on May 12, 2018.…”

Section: The Pc System In Vascular Inflammationmentioning

confidence: 99%

The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications

Danese

Vetrano

Zhang

et al. 2010

Blood

127

120

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Inflammation and coagulation are closely linked interdependent processes. Under physiologic conditions, the tissue microcirculation functions in anticoagulant and anti-inflammatory fashions. However, when inflammation occurs, coagulation is also set in motion and actively participates in enhancing inflammation. Recently, novel and unexpected roles of hemostasis in the humoral and cellular components of innate immunity have been described. In particular, the protein C system, besides its well-recognized role in anticoagulation, plays a crucial role in inflammation. Indeed, the protein C system is now emerging as a novel participant in the pathogenesis of acute and chronic inflammatory diseases, such as sepsis, asthma, inflammatory bowel disease, atherosclerosis, and lung and heart inflammation, and may emerge as unexpected therapeutic targets for intervention. (Blood.

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Activated protein C and ischemic stroke

Abstract: There is compelling evidence that ischemic stroke is an attractive target for therapy with APC.

Cited by 45 publications

References 52 publications

Activated Protein C Protects Against Myocardial Ischemia/ Reperfusion Injury via Inhibition of Apoptosis and Inflammation

Activated Protein C Protects Against Myocardial Ischemia/ Reperfusion Injury via Inhibition of Apoptosis and Inflammation

The cytoprotective protein C pathway

The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications

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