Prostaglandin receptors EP2 and IP are detectable in atherosclerotic arteries and plaques.
OBJECTIVE
Prostaglandin (PG) receptor agonists are frequently used for the pharmacological treatment of arteriosclerosis obliterans (ASO). In particular, the PG receptors EP2 and IP stimulate vasodilation and inhibit platelet aggregation, biological processes thought to be protective against ASO and important for physiological homeostasis. However it is uncertain whether EP2 and IP exist in diseased arteries, or what their distribution within the artery might be. In this study, we analyzed the distribution of these PG receptors in patients with severe ASO to determine the potential application of stimulation of these receptors as targets for pharmacological treatment.


METHODS
We collected segments of atherosclerotic femoral arteries during femoropopliteal bypass surgery and determined the expression levels of EP2 and IP receptors by western blotting. Immunofluorescence was used to observe receptor localization.


RESULTS
Findings of western blotting showed an increased Cox-2 expression in patients with ASO. The EP2 as well as IP receptors were each induced approximately 3-fold in comparison to normal samples. The expression of these receptors was increased in the intimal layer as well as the medial layer; their expression was also detectable within the atherosclerotic plaque.


CONCLUSIONS
We observed induction of the PG receptors EP2 and IP in atherosclerotic femoral arteries in the arterial intima, medial layer, as well as the associated atherosclerotic plaque. These results suggest that receptor-selective PG agonists specifically target atherosclerotic arteries and therefore, may find potential application in the pharmacological management of patients with ASO.
Muto
A
A
Section of Vascular Surgery, Yale University School of Medicine, New Haven, CT, USA.
Nishibe
T
T
Miyauchi
Y
Y
Kondo
Y
Y
Yamamoto
Y
Y
Dardik
A
A
Shigematsu
H
H
D001162:Arteriosclerosis Obliterans / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D005263:Femoral Artery / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D006801:Humans; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000032:analysis*; D018078:Receptors, Prostaglandin E / Q000032:analysis*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D017539:Tunica Intima / Q000737:chemistry*; D017540:Tunica Media / Q000737:chemistry*; D015854:Up-Regulation
C545644:PTGER2 protein, human; C113936:PTGIR protein, human; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype