Elevated platelet angiostatin and circulating endothelial microfragments in idiopathic pulmonary arterial hypertension: a preliminary study.
BACKGROUND
Idiopathic pulmonary arterial hypertension (IPAH) is characterized by pulmonary arteriolar narrowing and degeneration associated with in situ thrombosis. We hypothesized that microvascular endothelial injury and apoptosis may be an initiating mechanism in IPAH. Endothelial apoptosis generates endothelial microfragments (EMF), which can activate platelets. Platelets release both VEGF and angiostatin, which depending the balance can inhibit or induce endothelial apoptosis, respectively.


METHODS
We measured EMFs from blood of IPAH patients as index of endothelial cell apoptosis/injury and levels of pro- and anti- EC apoptotic factors found in platelets. EMFs and platelets in blood samples from control subjects and patients with IPAH were measured using a 4-color flow cytometry protocol, and platelet levels of VEGF and angiostatin were determined by ELISAs and immunoblotting.


RESULTS
Compared to controls, IPAH patients exhibited higher numbers of circulating EMFs and more activated/apoptotic platelets. IPAH patients also exhibited higher levels of platelet angiostatin; however, no significant difference was detected in platelet VEGF levels between the two groups.


CONCLUSIONS
These results are consistent with an increase in EC dysfunction in patients with IPAH, possibly contributing to the progression of IPAH and its associated thrombosis.
St. Michael's Hospital, Toronto; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. pjurasz@pharmacy.ualberta.ca
Paul
P
Jurasz
Douglas
D
Ng
John T
JT
Granton
David W
DW
Courtman
Duncan J
DJ
Stewart
D000328:Adult; D000368:Aged; D043168:Angiostatins / Q000502:physiology*; D001792:Blood Platelets / Q000737:chemistry*; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000502:physiology; D004727:Endothelium / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000503:physiopathology*
D043168:Angiostatins