Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart.

نویسندگان

  • Jiang Yang
  • Steven P Jones
  • Toshimitsu Suhara
  • James J M Greer
  • Paul D Ware
  • Nhan P Nguyen
  • Harris Perlman
  • David P Nelson
  • David J Lefer
  • Kenneth Walsh
چکیده

Fas ligand (FasL) is a member of tumor necrosis factor family that induces apoptosis in target cells that express Fas. The function of FasL during inflammation remains controversial. In this study, we examined the role of vascular endothelial FasL during acute myocardial ischemia-reperfusion that is closely associated with inflammation. Transgenic mouse lines were established that overexpress human FasL on endothelium under the control of the vascular endothelial cadherin promoter. Expression of FasL transgene was detected at both mRNA and protein levels, and functional transgene-encoded FasL protein was specifically expressed on the surface of vascular endothelial cells. Transgenic mice developed normally and had normal hearts. When subjected to 30 min of myocardial ischemia and 72 h of reperfusion, myocardial infarct size was reduced by 42% in the transgenic mice compared with nontransgenic littermates (p < 0.05). Moreover, hemodynamic data demonstrated that transgenic hearts performed better following ischemia and reperfusion compared with nontransgenic hearts. Myocardial neutrophil infiltration was reduced by 54% after 6 h of reperfusion in transgenic hearts (p < 0.01). Neutrophil depletion prior to ischemia-reperfusion injury led to smaller infarcts that were not different between transgenic and nontransgenic mice, suggesting that endothelial FasL may attenuate ischemia-reperfusion injury by abating the inflammatory response. These results indicate that vascular endothelial FasL may exert potent anti-inflammatory actions in the setting of myocardial ischemia-reperfusion injury.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effects of normobaric hyperoxia pretreatment on ischemia-reperfusion injury in regional ischemia model of isolated rat heart

Abstract Introduction: Resent studies have been shown beneficial effects of hyperoxia pretreatment against ischemia-reperfusion injury in different organs. The aim of the present study was to investigate early and late effects of normobaric hyperoxia (≥95% O2) pretreatment on ischemia-reperfusion injuries in isolated rat hearts. Methods: Following 60 and 180 minutes of hyperoxia, rat hearts w...

متن کامل

Methanolic leaf extract of Punica granatum attenuates ischemia-reperfusion brain injury in Wistar rats: Potential antioxidant and anti-inflammatory mechanisms

Objective(s): This study was conducted to evaluate the cerebroprotective effect of methanolic leaf extract of Punica granatum (MePG) in Wistar rats.Materials and Methods: The MePG was initially assessed for in vitro antioxidant activity, and later evaluated on LPS-induced RAW 264.7 cell line assay. Finally, the MePG was evaluated against ischemia-reperfusion (I/R) induced brain injury in Wistar...

متن کامل

Overexpression of human copper/zinc superoxide dismutase (SOD1) suppresses ischemia-reperfusion injury and subsequent development of graft coronary artery disease in murine cardiac grafts.

BACKGROUND Ischemia-reperfusion injury is an important risk factor for graft coronary artery disease (GCAD). We hypothesized that overexpression of SOD1 in donor hearts would suppress ischemia-reperfusion injury and thereby reduce GCAD. METHODS AND RESULTS In one series, donor hearts of C57BL/6 (H-2b) transgenic mice overexpressing human SOD1 or C57BL/6 wild-type mice were heterotopically tra...

متن کامل

Involvement of CD95/Apo1/Fas in cell death after myocardial ischemia.

BACKGROUND The death of cardiac cells during ischemia and reperfusion is partially mediated by apoptosis, as seen, eg, in autopsy material of patients after acute myocardial infarction. METHODS AND RESULTS To study the role of CD95/Fas/Apo1 for induction of postischemic cell death, we used an ischemia/reperfusion model of isolated rat and mouse hearts in Langendorff perfusion. In this model, ...

متن کامل

Candesartan Attenuates Ischemic Brain Edema and Protects the Blood–Brain Barrier Integrity from Ischemia/Reperfusion Injury in Rats

Background: Angiotensin II (Ang II) has an important role on cerebral microcirculation however, its direct roles in terms of ischemic brain edema need to be clarified. This study evaluated the role of central Ang II by using candesartan, as an AT1 receptor blocker, in the brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia/reperfusion (I/R) injuries in rat. Methods...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of biological chemistry

دوره 278 17  شماره 

صفحات  -

تاریخ انتشار 2003