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Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12001/24350

Title :Telmisartan inhibits PAI-1 mRNA expression independently of peroxisome proliferator-activated receptor γ in vascular endothelial cells
Authors :Uehara, Ken
Sunagawa, Masanori
Nakamura-Higa, Mariko
Suzuki, Mikio
Kosugi, Tadayoshi
Authors affiliation :Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
Department of Nursing, Graduate School of Nursing, Meio University, Okinawa, Japan
Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
Nago Memorial Clinic, Okinawa
Issue Date :2018
Publisher :琉球医学会
Type Local :雑誌掲載論文
Type (NII) :Journal Article
ISSN :1346-888X
Abstract :To investigate whether telmisartan (TMS), a unique angiotensin II type 1 receptor(AT1R) antagonist with selective peroxisome proliferator-activated receptor (PPAR) γ- modulating activity, inhibits plasminogen activator inhibitor 1 (PAI-1) and/or stimulates issue-type plasminogen activator (t-PA) mRNA expression in vascular endothelial cells(VECs), we cultured VECs obtained from the thoracic aorta of Long Evans Tokushima Otsuka rats by the explant method. mRNA expression was measured using comparative reverse transcription polymerase chain reaction. The binding activity of PPARγ to its coactivator (CREB-binding protein) was determined by enzyme-linked immunosorbent assay. The synthetic PPARγ agonists troglitazone (TRO) and TMS activated PPARγ with EC_50 values of 0.95 and 161μM, respectively, under cell-free conditions. PPARγ mRNA was constitutively expressed in cultured VECs, unlike PPARα and PPARβ. PAI-1 mRNA expression was significantly downregulated by TMS, and this downregulation was not abolished by the presence of the PPARγ antagonist GW9662. The expression of t-PA mRNA was not altered by TMS treatment. TRO had no effect on PAI-1 and t-PA mRNA expressions.PAI-1 mRNA expression was significantly decreased by GW9662. In conclusion, TMS inhibited PAI-1 mRNA expression independently of PPARγ activation. Intrinsic PPARγ agonists, but not extrinsic PPARγ agonists, may be involved in basal mRNA expression of PAI-1 in VECs
Rights :琉球医学会
URI :http://hdl.handle.net/20.500.12001/24350
Citation :琉球医学会誌 = Ryukyu Medical Journal Vol.37 no.1-4 p.41 -50
Appears in Collections:Ryukyu Medical Journal

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