title: Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.
abstract: OBJECTIVE
  Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs).
  
  
  RESULTS
  In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK.
  
  
  CONCLUSIONS
  Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation.
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Hirofumi
authors: H
authors: Kurokawa
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan. Electronic address: ssugiyam@kumamoto-u.ac.jp.
authors: Seigo
authors: S
authors: Sugiyama
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Toshimitsu
authors: T
authors: Nozaki
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Koichi
authors: K
authors: Sugamura
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Kensuke
authors: K
authors: Toyama
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Junichi
authors: J
authors: Matsubara
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Koichiro
authors: K
authors: Fujisue
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Keisuke
authors: K
authors: Ohba
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Hirofumi
authors: H
authors: Maeda
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Masaaki
authors: M
authors: Konishi
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Eiichi
authors: E
authors: Akiyama
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Hitoshi
authors: H
authors: Sumida
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Yasuhiro
authors: Y
authors: Izumiya
authors: Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Kumamoto University, Kumamoto, Japan.
authors: Osamu
authors: O
authors: Yasuda
authors: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Shokei
authors: S
authors: Kim-Mitsuyama
authors: Department of Cardiovascular Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Hisao
authors: H
authors: Ogawa
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000959:Antihypertensive Agents / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D017353:Gene Deletion; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D034622:RNA Interference; D000077333:Telmisartan; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D019001:Nitric Oxide Synthase; D055372:AMP-Activated Protein Kinases; D001616:beta-Galactosidase; D000077333:Telmisartan
keywords: AMPK; Endothelial function; Mitochondria; Senescence; eNOS