eNOS, COX-2, and prostacyclin production are impaired in endothelial cells from diabetics.
The vascular endothelium is a well-recognized target of damage for factors leading to increased cardiovascular risk. Among the agents playing an important role in cardiovascular homeostasis, nitric oxide and prostacyclin represent key markers of endothelial integrity. In the present work, we report for the first time the reduced expression of both endothelial nitric oxide synthase and cyclooxygenase-2 (COX-2) proteins, as well as decreased prostacyclin production, in unstimulated human endothelial cells from insulin-dependent diabetic mothers when compared to cells from non-diabetic, control subjects. According to a major role of COX-2 as a source of prostacyclin production even in unstimulated endothelial cells, prostacyclin production was concentration-dependently inhibited by the selective COX-2 inhibitor SC236. Overall, our results suggest a possible link between reduced endothelial COX-2 and NO-synthase expression and the increased risk of cardiovascular diseases affecting diabetic patients, and point to the use of endothelial cells from diabetic patients as a tool for investigating early dysfunction in pathological endothelium.
Bolego
Chiara
C
Department of Pharmacological Sciences, University of Milan, Italy.
Buccellati
Carola
C
Radaelli
Tatjana
T
Cetin
Irene
I
Puglisi
Lina
L
Folco
Giancarlo
G
Sala
Angelo
A
D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D000096926:Benzenesulfonamides
D051546:Cyclooxygenase 2; D011464:Epoprostenol; D008565:Membrane Proteins; D052250:Nitric Oxide Synthase Type III; D011720:Pyrazoles; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human