title: Altered arterial expression patterns of inducible and endothelial nitric oxide synthase in pulmonary plexogenic arteriopathy caused by congenital heart disease.
abstract: Flow-associated pulmonary hypertension leads to pulmonary plexogenic arteriopathy (PPA), a specific pulmonary vascular disease that includes vascular lesions characterized by abnormal vasodilatation and endothelial cell proliferation. Increased local production of NO has been suggested in this condition. Because reported data on the expression of endothelial NO-synthase (ecNOS) have been contradictory, we speculated that the expression of the inducible isoform of NOS (iNOS) is enhanced in this form of pulmonary hypertension. We investigated immunohistochemically the expression of ecNOS and iNOS in lung tissue of patients with flow-associated pulmonary hypertension (n = 18) and compared the findings with those in patients with increased pulmonary blood flow but normal pulmonary artery pressure (n = 10), with congestive vasculopathy (n = 6) and control subjects (n = 4). Immunoreactivity for ecNOS and iNOS was present both in normal and diseased pulmonary arteries. Marked immunoreactivity to both isoforms was present within the advanced lesions of PPA, including plexiform lesions. Semiquantitative analysis of immunoreactivity, both for ecNOS and iNOS, showed no correlation with the severity of morphologic vascular lesions (p = 0.29 and p = 0.23, respectively). In contrast to ecNOS, immunoreactivity for iNOS was increased in patients with flow-associated pulmonary hypertension compared with other patients (p = 0.02). The present study has demonstrated enhanced expression of iNOS in patients at risk for advanced PPA, but not in patients with other forms of pulmonary arteriopathy. Moreover, high expression of both ecNOS and iNOS were present in advanced lesions of PPA. These data suggest differentiated roles for different isoforms of NOS in the pathogenesis of this specific pulmonary arteriopathy.
authors.affiliation: Department of Pediatrics, Division of Pediatric Cardiology, Sophia Children's Hospital/University Hospital Rotterdam, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. berger@alkg.azr.nl
authors.forename: R M
authors.initials: RM
authors.lastname: Berger
authors.forename: R
authors.initials: R
authors.lastname: Geiger
authors.forename: J
authors.initials: J
authors.lastname: Hess
authors.forename: A J
authors.initials: AJ
authors.lastname: Bogers
authors.forename: W J
authors.initials: WJ
authors.lastname: Mooi
mesh_terms: D000704:Analysis of Variance; D001706:Biopsy; D001783:Blood Flow Velocity; D006328:Cardiac Catheterization; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000737:chemistry*; D006330:Heart Defects, Congenital / Q000150:complications*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II; D011651:Pulmonary Artery / Q000166:cytology*; D011652:Pulmonary Circulation; D011669:Pulmonary Wedge Pressure; D012307:Risk Factors
chemical_list: C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II