Expression and Cellular Localization of 15-Hydroxy-Prostaglandin-Dehydrogenase in Abdominal Aortic Aneurysm.
PGE2 has been implicated in abdominal aortic aneurysm (AAA) associated hypervascularization. PGE2-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 PGE2 secreted by aortic samples was significantly higher in AAA. AAA production of total PGE2 and PGE2 metabolites correlated positively with PGI2 production, while the percentage of metabolized PGE2 correlated negatively with the total amount of PGE2 and with PGI2. 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 PGE2 catabolism, reinforcing the potential role of microvasculature derived PGE2 in AAA-associated hypervascularization.
Autonomous University of Barcelona, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
David
D
Solà-Villà
Angiology, Vascular Biology and Inflammation Laboratory, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain; Vascular Surgery Department, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
Jaime-Félix
JF
Dilmé
Cardiovascular Research Center (CSIC-ICCC), Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
Cristina
C
Rodríguez
Angiology, Vascular Biology and Inflammation Laboratory, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain; Vascular Surgery Department, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
Begoña
B
Soto
Angiology, Vascular Biology and Inflammation Laboratory, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
Luis
L
Vila
Angiology, Vascular Biology and Inflammation Laboratory, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain; Vascular Surgery Department, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
José-Román
JR
Escudero
Cardiovascular Research Center (CSIC-ICCC), Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
José
J
Martínez-González
Angiology, Vascular Biology and Inflammation Laboratory, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain.
Mercedes
M
Camacho
D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000201:enzymology / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000201:enzymology / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques
D015415:Biomarkers; D012333:RNA, Messenger; D011464:Epoprostenol; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone