Expression and cellular localization of 15-hydroxy-prostaglandin-dehydrogenase in abdominal aortic aneurysm

Abstract

PGE 2 has been implicated in abdominal aortic aneurysm (AAA) associated hypervascularization. PGE 2 -metabolism involves 15-hydroxyprostaglandin-dehydrogenase (15-PGDH) the expression of which in AAA is unknown. The aim of this study was to examine the expression and cell distribution of 15-PGDH in AAA. Here, we show that 15-PGDH mRNA levels were significantly higher in aorta samples from patients undergoing AAA repair than in those from healthy multiorgan donors. Consequently, the ratio of metabolized PGE 2 secreted by aortic samples was significantly higher in AAA. AAA production of total PGE 2 and PGE 2 metabolites correlated positively with PGI 2 production, while the percentage of metabolized PGE 2 correlated negatively with the total amount of PGE 2 and with PGI 2. Transcript levels of 15-PGDH were statistically associated with leukocyte markers but did not correlate with microvascular endothelial cell markers. Immunohistochemistry revealed 15-PGDH in the areas of leukocyte infiltration in AAA samples, mainly associated with CD45-positive cells, but not in normal aorta samples. We provide new data concerning 15-PGDH expression in human AAA, showing that 15-PGDH is upregulated in AAA and mainly expressed in infiltrating leukocytes. Our data suggest that microvasculature was not involved in PGE 2 catabolism, reinforcing the potential role of microvasculature derived PGE 2 in AAA-associated hypervascularization.