title: Abnormal platelet aggregation in idiopathic pulmonary arterial hypertension: role of nitric oxide.
abstract: Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease. Several processes are believed to lead to the fatal progressive pulmonary arterial narrowing seen in IPAH including vasoconstriction, cellular proliferation inflammation, vascular remodeling, abnormalities in the lung matrix, and in situ thrombosis. Nitric oxide (NO) produced by NO synthases (NOS) is a potent vasodilator and plays important roles in many other processes including platelet function. Reduced NO levels in patients with IPAH are known to contribute to the development of pulmonary hypertension and its complications. Platelet defects have been implied in IPAH, but original research supporting this hypothesis has been limited. Normal platelets are known to have NOS activity, but little is known about NOS expression and NO production by platelets in patients with IPAH. Here we characterized the phenotype of the platelets in IPAH and show a defect in their ability to be activated in vitro by thrombin receptor activating protein but not adenosine diphosphate. We also show that endothelial NOS (eNOS) levels in these platelets are reduced and demonstrate that NO is an important regulator of platelet function. Thus reduced levels of eNOS in platelets could impact their ability to regulate their own function appropriately.
authors.affiliation: Department of Pathobiology/Lerner Research Institute, Cleveland Clinic, OH 44195, USA.
authors.forename: Metin
authors.initials: M
authors.lastname: Aytekin
authors.forename: Kulwant S
authors.initials: KS
authors.lastname: Aulak
authors.forename: Sarah
authors.initials: S
authors.lastname: Haserodt
authors.forename: Ritu
authors.initials: R
authors.lastname: Chakravarti
authors.forename: Joseph
authors.initials: J
authors.lastname: Cody
authors.forename: Omar A
authors.initials: OA
authors.lastname: Minai
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010974:Platelet Aggregation / Q000235:genetics / Q000502:physiology*; D010976:Platelet Count / Q000379:methods; D011651:Pulmonary Artery / Q000378:metabolism* / Q000503:physiopathology*; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology
chemical_list: D010446:Peptide Fragments; C086309:thrombin receptor peptide SFLLRNP; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III