title: Telmisartan modulates mitochondrial function in vascular smooth muscle cells.
abstract: The development of atherosclerosis is associated with disturbances in mitochondrial function that impair effective adenosine triphosphate (ATP) production, increase generation of superoxide and induce subsequent apoptosis in vascular smooth muscle cells (VSMCs). As peroxisome proliferator-activated receptor gamma (PPARγ) has a potentially important role in the regulation of mitochondrial metabolism, we studied effects of the partial PPARγ agonist and angiotensin receptor blocker telmisartan, on mitochondria-related cellular responses in VSMC. In human VSMC, telmisartan increased ATP levels and activation of mitochondrial complex II, succinate dehydrogenase, reduced the release of H2O2 and attenuated H2O2-induced increases in caspase 3/7 activity, a marker of cellular apoptosis. Eprosartan, an angiotensin II receptor blocker that lacks the ability to activate PPARγ, had no effect on these mitochondria-related cellular responses in VSMC. Studies in PPARγ-deficient VSMC revealed that the effects of telmisartan on mitochondrial function were largely independent of PPARγ although the presence of PPARγ modulated effects of telmisartan on H2O2 levels. These findings demonstrate that telmisartan can have significant effects on mitochondrial metabolism in VSMC that are potentially relevant to the pathogenesis of cardiovascular disease and that involve more than just angiotensin receptor blockade and activation of PPARγ.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kiyo
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohishi
authors.forename: Hikari
authors.initials: H
authors.lastname: Takeshita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hongyo
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawai
authors.forename: Masao
authors.initials: M
authors.lastname: Takeda
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured; D056915:DNA Copy Number Variations / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000172:deficiency / Q000378:metabolism; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000077333:Telmisartan