title: Decreased vasorelaxation induced by iloprost during acute inflammation in human internal mammary artery.
abstract: Cyclooxygenase-2 (COX-2) induction in human internal mammary arteries (IMA) under inflammatory conditions has been associated with attenuated norepinephrine (NE)-induced vasoconstriction. This effect was associated with increased prostaglandin (PG) E2and prostacyclin (PGI2) releases. The present study was designed to assess the role of these PG and their receptors (EP and IP, respectively) on the vascular reactivity during acute inflammation. Isolated IMA were cultured in the absence (Control conditions) or presence (Inflammatory conditions) of both interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS). The vasorelaxation and the increased content of cyclic adenosine monophosphate (cAMP) induced by iloprost, a PGI2analogue, were significantly reduced under inflammatory conditions and restored in preparations cultured with the IP antagonist (CAY10441). Decreased cAMP levels under inflammatory conditions are due to at least increased phosphodiesterase (PDE) 4B expression. On the other hand, PGE2, thromboxane analogues and EP agonists-induced vasoconstrictions were not affected under inflammatory conditions. No vasorelaxation was observed with PGD2, PGE2or the EP2/4 agonists in pre-contracted IMA. Finally, using RT-qPCR and immunohistochemistry, the COX-2, IP receptor and PGI2synthase (PGIS) were detected. A significant increase of COX-2 and moderate increase of IP mRNA expression was observed under inflammatory conditions, whereas PGIS mRNA level was not affected. This study demonstrates that PGI2/IP receptor signalling and PGI2-induced relaxation are impaired in human IMA during acute inflammation, whereas the responses induced by other prostanoids are not affected. These results could explain some of the mechanisms of vascular dysfunction reported in inflammatory conditions.
authors.affiliation: Laboratoire des maladies cardiovasculaires d'origine génétique et nutritionnelle, University Setif 1, Algeria; Department of Pharmacy, Faculty of Medicine, University Setif 1, Algeria.
authors.forename: Nabil
authors.initials: N
authors.lastname: Foudi
authors.affiliation: INSERM U1148, CHU X. Bichat, Université Paris Nord, Sorbonne Paris Cité, Paris, France.
authors.forename: Gulsev
authors.initials: G
authors.lastname: Ozen
authors.affiliation: INSERM U1148, CHU X. Bichat, Université Paris Nord, Sorbonne Paris Cité, Paris, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Amgoud
authors.affiliation: INSERM U1148, CHU X. Bichat, Université Paris Nord, Sorbonne Paris Cité, Paris, France.
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.affiliation: INSERM U1148, CHU X. Bichat, Université Paris Nord, Sorbonne Paris Cité, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Choqueux
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University Setif 1, Algeria.
authors.forename: Aouatef
authors.initials: A
authors.lastname: Badi
authors.affiliation: INSERM, U1149, CNRS ERL8252, Centre de Recherche sur l'Inflammation, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Site Bichat, Paris, France.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kotelevets
authors.affiliation: INSERM, U1149, CNRS ERL8252, Centre de Recherche sur l'Inflammation, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Site Bichat, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chastre
authors.affiliation: INSERM U1148, CHU X. Bichat, Université Paris Nord, Sorbonne Paris Cité, Paris, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Longrois
authors.affiliation: INSERM U1148, CHU X. Bichat, Université Paris Nord, Sorbonne Paris Cité, Paris, France. Electronic address: xnorel@hotmail.com.
authors.forename: Xavier
authors.initials: X
authors.lastname: Norel
mesh_terms: D000208:Acute Disease; D000368:Aged; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D011453:Prostaglandins / Q000819:agonists; D011982:Receptors, Prostaglandin / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D016285:Iloprost
keywords: Human mammary artery; Iloprost; Inflammation; PGE(2); PGI(2); Vasorelaxation