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Compensatory mechanisms to overcome a chronic endothelial nitric oxide deficit
Author(s) -
Hecker Markus,
Yakubenia Sviatlana,
Rumig Cordula,
Asif Abdulrahman,
Cattaruzza Marco
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.116.11
Subject(s) - nitric oxide synthase , endothelial dysfunction , endothelial nitric oxide synthase , nitric oxide , cyclooxygenase , nitric oxide synthase type iii , prostaglandin , atp synthase , chemistry , phenotype , endocrinology , gene , microbiology and biotechnology , medicine , biology , enos , biochemistry , enzyme
Nitric oxide (NO) is fundamentally important for endothelial cell (EC) function. Using a genetically determined defect in NO formation, the T‐786C single nucleotide polymorphism of the human endothelial NO synthase gene ( NOS3 ), we have now characterized two compensatory mechanisms providing resistance against the development of endothelial dysfunction due to NO deficiency. EC expression of the NOS3 gene usually is maintained by fluid shear stress (FSS) generated through the flowing blood. This FSS‐induced NO synthase expression, however, is much less efficient in EC with a −786 CC NOS3 genotype. Although these cells consequently produce little NO, they exhibit quite a stable phenotype. Thus they express high levels of manganese superoxide dismutase, thereby protecting NO from degradation. Moreover, they respond to FSS with an increased expression of cyclooxygenase‐2 and prostaglandin D synthase, reinforcing the formation of prostaglandins D 2 and J 2 which strongly inhibit leukocyte transmigration through −786 CC genotype EC monolayers. These are possibly only two examples by which EC with a chronic deficit in NO formation fight off endothelial dysfunction and hence effectively delay the onset of atherosclerosis. Supported by the Deutsche Forschungsgemeinschaft (grant no. HE 1587/9‐2).