title: Reverse Regulatory Pathway (H2S / PGE2 / MMP) in Human Aortic Aneurysm and Saphenous Vein Varicosity.
abstract: Hydrogen sulfide (H2S) is a mediator with demonstrated protective effects for the cardiovascular system. On the other hand, prostaglandin (PG)E2 is involved in vascular wall remodeling by regulating matrix metalloproteinase (MMP) activities. We tested the hypothesis that endogenous H2S may modulate PGE2, MMP-1 activity and endogenous tissue inhibitors of MMPs (TIMP-1/-2). This regulatory pathway could be involved in thinning of abdominal aortic aneurysm (AAA) and thickening of saphenous vein (SV) varicosities. The expression of the enzyme responsible for H2S synthesis, cystathionine-γ-lyase (CSE) and its activity, were significantly higher in varicose vein as compared to SV. On the contrary, the endogenous H2S level and CSE expression were lower in AAA as compared to healthy aorta (HA). Endogenous H2S was responsible for inhibition of PGE2 synthesis mostly in varicose veins and HA. A similar effect was observed with exogenous H2S and consequently decreasing active MMP-1/TIMP ratios in SV and varicose veins. In contrast, in AAA, higher levels of PGE2 and active MMP-1/TIMP ratios were found versus HA. These findings suggest that differences in H2S content in AAA and varicose veins modulate endogenous PGE2 production and consequently the MMP/TIMP ratio. This mechanism may be crucial in vascular wall remodeling observed in different vascular pathologies (aneurysm, varicosities, atherosclerosis and pulmonary hypertension).
authors.affiliation: INSERM, U1148, Paris, 75018, France.|University Paris Nord, UMR-S1148, Paris, 75018, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gomez
authors.affiliation: INSERM, U1148, Paris, 75018, France.|Istanbul University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
authors.forename: Gulsev
authors.initials: G
authors.lastname: Ozen
authors.affiliation: INSERM, U1148, Paris, 75018, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Deschildre
authors.affiliation: INSERM, U1148, Paris, 75018, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Amgoud
authors.affiliation: INSERM, U1148, Paris, 75018, France.
authors.forename: Lilia
authors.initials: L
authors.lastname: Boubaya
authors.affiliation: AP-HP CHU X. Bichat, Department of Anesthesia and Intensive Care, University Paris Diderot, Sorbonne Paris-Cité, UMR-S1148, Paris, 75018, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gorenne
authors.affiliation: INSERM, U1148, Paris, 75018, France.|University Paris Nord, UMR-S1148, Paris, 75018, France.
authors.forename: Chabha
authors.initials: C
authors.lastname: Benyahia
authors.affiliation: UMR 8601, LCBPT, CNRS-Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roger
authors.affiliation: INSERM, U1148, Paris, 75018, France.|AP-HP CHU X. Bichat, Department of Vascular and Thoracic Surgery, University Paris Diderot, Sorbonne Paris-Cité, UMR-S1148, Paris, 75018, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Lesèche
authors.affiliation: UMR 8601, LCBPT, CNRS-Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Galardon
authors.affiliation: Istanbul University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkey.
authors.forename: Gokce
authors.initials: G
authors.lastname: Topal
authors.affiliation: INSERM, U1148, Paris, 75018, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Jacob
authors.affiliation: INSERM, U1148, Paris, 75018, France.|AP-HP CHU X. Bichat, Department of Anesthesia and Intensive Care, University Paris Diderot, Sorbonne Paris-Cité, UMR-S1148, Paris, 75018, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Longrois
authors.affiliation: INSERM, U1148, Paris, 75018, France.|University Paris Nord, UMR-S1148, Paris, 75018, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Norel
mesh_terms: D000368:Aged; D001014:Aortic Aneurysm / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D012501:Saphenous Vein / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D013447:Sulfites / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014648:Varicose Veins / Q000378:metabolism* / Q000473:pathology
chemical_list: D013447:Sulfites; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D045726:Metalloproteases; D015232:Dinoprostone; C042345:hydrogen sulfite