BACKGROUND: Inducible nitric oxide synthase (iNOS, or NOS2) reduces the severity of accelerated graft arteriosclerosis (AGA) in transplanted organs, although the precise mechanism is unclear. METHODS AND RESULTS: We transplanted wild-type murine hearts into either wild-type or NOS2-null recipient mice; we then measured cardiac allograft survival and analyzed tissue sections by immunohistochemistry. We have confirmed that NOS2 increases cardiac allograft survival. We now show that there is less inflammation of cardiac allografts in wild-type hosts than in NOS2-null hosts. Furthermore, staining for von Willebrand factor reveals that the presence of NOS2 is correlated with the presence of Weibel-Palade bodies inside endothelial cells, whereas the absence of NOS2 is correlated with the release of Weibel-Palade bodies. CONCLUSIONS: Weibel-Palade bodies contain mediators that promote thrombosis and inflammation. Therefore, nitric oxide (NO) may stabilize the vessel wall and prevent endothelial activation in part by inhibiting the release of the contents of Weibel-Palade bodies. Prevention of Weibel-Palade body release might be a mechanism by which NO protects the vessel wall from inflammatory disorders such as atherosclerosis or graft arteriosclerosis.
BACKGROUND:Inducible nitric oxide synthase (iNOS, or NOS2) reduces the severity of accelerated graft arteriosclerosis (AGA) in transplanted organs, although the precise mechanism is unclear. METHODS AND RESULTS: We transplanted wild-type murine hearts into either wild-type or NOS2-null recipient mice; we then measured cardiac allograft survival and analyzed tissue sections by immunohistochemistry. We have confirmed that NOS2 increases cardiac allograft survival. We now show that there is less inflammation of cardiac allografts in wild-type hosts than in NOS2-null hosts. Furthermore, staining for von Willebrand factor reveals that the presence of NOS2 is correlated with the presence of Weibel-Palade bodies inside endothelial cells, whereas the absence of NOS2 is correlated with the release of Weibel-Palade bodies. CONCLUSIONS: Weibel-Palade bodies contain mediators that promote thrombosis and inflammation. Therefore, nitric oxide (NO) may stabilize the vessel wall and prevent endothelial activation in part by inhibiting the release of the contents of Weibel-Palade bodies. Prevention of Weibel-Palade body release might be a mechanism by which NO protects the vessel wall from inflammatory disorders such as atherosclerosis or graft arteriosclerosis.
Authors: Munekazu Yamakuchi; James J M Greer; Scott J Cameron; Kenji Matsushita; Craig N Morrell; Karen Talbot-Fox; William M Baldwin; David J Lefer; Charles J Lowenstein Journal: Circ Res Date: 2005-05-19 Impact factor: 17.367
Authors: Gaynor Aguilar; Francisco Córdova; Tania Koning; José Sarmiento; Mauricio P Boric; Konstantin Birukov; Jorge Cancino; Manuel Varas-Godoy; Andrea Soza; Natascha G Alves; Patricio E Mujica; Walter N Durán; Pamela Ehrenfeld; Fabiola A Sánchez Journal: Am J Physiol Heart Circ Physiol Date: 2021-10-15 Impact factor: 4.733
Authors: S Leah Etheridge; Michelle E Roh; Megan E Cosgrove; Veena Sangkhae; Norma E Fox; Junmei Chen; José A López; Kenneth Kaushansky; Ian S Hitchcock Journal: Proc Natl Acad Sci U S A Date: 2014-01-27 Impact factor: 11.205
Authors: Kenji Matsushita; Craig N Morrell; Beatrice Cambien; Shui Xiang Yang; Munekazu Yamakuchi; Clare Bao; Makoto R Hara; Richard A Quick; Wangsen Cao; Brian O'Rourke; John M Lowenstein; Jonathan Pevsner; Denisa D Wagner; Charles J Lowenstein Journal: Cell Date: 2003-10-17 Impact factor: 41.582