Strong reduction of low-density lipoprotein receptor/apolipoprotein e expressions by telmisartan in cerebral cortex and hippocampus of stroke resistant spontaneously hypertensive rats

Yun Zhai, Toru Yamashita, Tomoko Kurata, Yusuke Fukui, Kota Sato, Syoichiro Kono, Wentao Liu, Yoshio Omote, Nozomi Hishikawa, Kentaro Deguchi, Koji Abe

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Telmisartan is a unique angiotensin II type 1 receptor blocker with a partial peroxisome proliferator-Activated receptorγ (PPARγ) agonistic property to exert not only antihypertensive effect but also antimetabolic syndrome effect.

Methods: We examined the long-term effect of telmisartan on cholesterol transport-related proteins (low-density lipoprotein receptor [LDL-R]/apolipoprotein E [ApoE]) and microtubule-Associated proteins 2 (MAP2) in the brains of stroke resistant spontaneously hypertensive rats (SHR-SRs), which were divided into 3 experiment groups including vehicle group (SHR/Ve), low-dose telmisartan group (SHR/Low, .3 mg/kg/day), and high-dose telmisartan group (SHR/High, 3 mg/kg/day).

Results: The numbers of LDL-R and immuno-ApoEpositive neurons increased in both cerebral cortex and hippocampus of SHR/Ve throughout 6, 12, and 18 months of age, compared with age-matched normotensiveWistar rats. On the other hand, telmisartan significantly reduced the numbers of LDL-R and ApoE immuno-positive neurons in both cerebral cortex and hippocampus, with similar effectiveness in the SHR/Low group without blood pressure (BP) lowering to BP lowering (SHR/High). The decrease of MAP2-positive neuron in SHR/Ve was recovered by telmisartan in both cerebral cortex and hippocampus.

Conclusions: These findings suggest that a long-term treatment with telmisartan directly improved neuronal lipid metabolism in the cerebral cortex and hippocampus of SHR-SR, mainly improving LDL-R and ApoE metabolism (SHR/Low) with a small additive benefit by BP lowering (SHR/High), which could provide a preventative approach in patients with hypertension at risk of Alzheimer disease.

Original languageEnglish
Pages (from-to)2350-2361
Number of pages12
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number9
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Alzheimer's disease
  • ApoE
  • LDL-R
  • spontaneously hypertensive rat
  • telmisartan

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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