Avtor/Urednik     Ljuca, Farid; Drevenšek, Gorazd
Naslov     Endothelin-1 induced vascular smooth muscle cell proliferation is mediated by cytochrome p-450 arachidonic acid metabolites
Tip     članek
Vir     Bosn J Basic Med Sci
Vol. in št.     Letnik 10, št. 3
Leto izdaje     2010
Obseg     str. 223-6
ISSN     1512-8601
Jezik     eng
Abstrakt     Endothelins (ETs) are a family of three peptides (ET-1, ET-2, ET-3) that are implicated in the physiological control of vascular smooth muscle cell (VSMC) and myocardial contractility and growth. ET-1 is vasoactive peptide that acts via ET-A receptors coupling inducing vascular smooth muscle cell contraction. ET-1 is involved in the development and maintenance of hypertension. Aim of this study was to investigate whether ET-1 can induce vascular smooth muscle cell proliferation through arachidonic acid (AA) metabolites formed via cytochrome P not450 (CYP-450). VSMC proliferation was measured by [3H]thymidine incorporation in cultured cells treated by ET-1 (10 to l00 nmol/L) in presence of different inhibitors of CYP-450 (17-ODYA 5 mumol/L), lipoxygenase (LO) (baicalein 20 mumol/L) and cyclooxygenase (COX) (indomethacin 5 mumol/L). ET-1 (10 to 100 nmol/L) induced VSMC proliferation and this effect was attenuated by CYP-450 inhibitor (17-ODYA) and lipoxygenase (LO) inhibitor (baicalein) but not by cyclooxygenase (COX) inhibitor (indomethacin). CYP-450 and LO metabolites of AA, 20-hydroxyeicosatetraenoic acid (HETE) and 12-HETE increased [3H]thymidine incorporation in VSMC. Inhibitors of MAP kinase (PD-98059 50 mumol/L) and cPLA2 (MAFP 50 mumol/L) attenuated ET-1 as well as 20-HETE induced VSMC proliferation. These results suggest AA metabolites via CYP-450 mediates ET-1 induce VSMC proliferation.
Deskriptorji     MUSCLE, SMOOTH
ENDOTHELIUM, VASCULAR
CELL DIVISION
ENDOTHELIN-1
CYTOCHROME P-450
LIPOXYGENASE INHIBITORS
ANALYSIS OF VARIANCE
12-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID
ARACHIDONIC ACID
CELLS, CULTURED
CYCLOOXYGENASE INHIBITORS
DNA
ENZYME INHIBITORS
HYDROXYEICOSATETRAENOIC ACIDS
INDOMETHACIN
RATS
THYMIDINE