Abstract
BackgroundIdiopathic pulmonary arterial hypertension (IPAH) is a devastating disease characterized by increased pulmonary vascular resistance, smooth muscle and endothelial cell proliferation, perivascular inflammatory infiltrates, and in situ thrombosis. Circulating intravascular ATP, ADP, AMP and adenosine activate purinergic cell signaling pathways and appear to induce many of the same pathologic processes that underlie IPAH. Extracellular dephosphorylation of ATP to ADP and AMP occurs primarily via CD39 (ENTPD1), an ectonucleotidase found on the surface of leukocytes, platelets, and endothelial cells [1]. Microparticles are micron-sized phospholipid vesicles formed from the membranes of platelets and endothelial cells. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease.Methodology/ Principal FindingsKinetic parameters, inhibitor blocking experiments, and immunogold labeling with electron microscopy support the role of CD39 as a major nucleotidase on the surface of microparticles. Comparison of microparticle surface CD39 expression and nucleotidase activity in 10 patients with advanced IPAH and 10 healthy controls using flow cytometry and thin layer chromatograph demonstrate the following: 1) circulating platelet (CD39+CD31+CD42b+) and endothelial (CD39+CD31+CD42b−) microparticle subpopulations in patients with IPAH show increased CD39 expression; 2) microparticle ATPase and ADPase activity in patients with IPAH is increased.Conclusions/ SignificanceWe demonstrate for the first time increased CD39 expression and function on circulating microparticles in patients with IPAH. Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH.
Highlights
Idiopathic pulmonary artery hypertension (IPAH) is a devastating disease of unclear etiology that results in rightsided heart failure, low cardiac output and death
Continued investigation into the mechanisms leading to the development of Idiopathic pulmonary arterial hypertension (IPAH) is of paramount importance. In addition to their roles as intracellular energy transporters, the purine nucleotides ATP, ADP, and AMP are important extracellular signaling molecules [5]. Such purinergic signaling is vital to the regulation of processes including vessel tone [6], apoptosis [7], smooth muscle and endothelial cell proliferation [8], platelet aggregation [9], and inflammation [10]; many of the same processes that are dysregulated in IPAH
The medical, functional and hemodynamic characteristics of individuals with IPAH are described in Tables 1 and 2 and are consistent with advanced pulmonary arterial hypertension
Summary
Idiopathic pulmonary artery hypertension (IPAH) is a devastating disease of unclear etiology that results in rightsided heart failure, low cardiac output and death. Continued investigation into the mechanisms leading to the development of IPAH is of paramount importance In addition to their roles as intracellular energy transporters, the purine nucleotides ATP, ADP, and AMP are important extracellular signaling molecules [5]. Such purinergic signaling is vital to the regulation of processes including vessel tone [6], apoptosis [7], smooth muscle and endothelial cell proliferation [8], platelet aggregation [9], and inflammation [10]; many of the same processes that are dysregulated in IPAH. Objectives: Studies here examine whether CD39 is an important microparticle surface nucleotidase, and whether patients with IPAH have altered microparticle-bound CD39 activity that may contribute to the pathophysiology of the disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
