Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein e knockout mice

Jong Ho Kim, I. Rang Lim, Hyung Joon Joo, Chi Yeon Park, Seung Cheol Choi, Han Saem Jeong, Soon Jun Hong

Research output: Contribution to journalArticle

Abstract

Background: The beneficial effects of angiotensin II type 1 receptor blockers (ARBs) on atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan on reducing neointimal formation and systemic inflammation after carotid artery (CA) injury in Apolipoprotein E knockout (ApoE KO) mice. Methods: ApoE KO mice were randomly allocated to Group I (without CA injury), Group II (without CA injury + Fimasartan), Group III (CA injury), and Group IV (CA injury + Fimasartan). Fimasartan was orally administered everyday starting 3 days before iatrogenic left CA injury. Results: At 28 days, neointimal hyperplasia and the inflammatory cytokines including TNFα, IL-6, ICAM, and MMP-9 in the peripheral blood were significantly reduced in Groups II and IV compared to Groups I and III, respectively. All fimasartan-administered groups revealed significant increases of CD4+CD25+Foxp3+ regulatory T (Treg) cells with increased plasma levels of IL-10 and TGFβ. In addition, increased CD8+ T cells by fimasartan were correlated with reduced smooth muscle cell (SMC) proliferation in the neointima in Groups II and IV. Furthermore, the populations of Treg and CD8+ T cells in total splenocytes were increased in Groups II and IV compared to Groups I and III, respectively. The enlargement of spleens due to CA injury in the Group III was attenuated by fimasartan, as shown in the Group IV. These data indicate that fimasartan significantly reduced SMC proliferation in neointima and increased Treg cells in ApoE KO CA injury mice. Conclusions: This study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation.

Original languageEnglish
Article number33
JournalMolecular Medicine
Volume25
Issue number1
DOIs
Publication statusPublished - 2019 Jul 15

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Carotid Artery Injuries
Apolipoproteins
Knockout Mice
Inflammation
Wounds and Injuries
Apolipoproteins E
Regulatory T-Lymphocytes
Neointima
Smooth Muscle Myocytes
Cell Proliferation
T-Lymphocytes
Angiotensin II Type 1 Receptor Blockers
fimasartan
Matrix Metalloproteinases
Interleukin-10
Hyperplasia
Interleukin-6
Atherosclerosis
Spleen
Cytokines

Keywords

  • Angiotensin receptor blockers
  • Atherosclerosis
  • Fimasartan
  • Neointimal hyperplasia
  • Regulatory T cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein e knockout mice. / Kim, Jong Ho; Lim, I. Rang; Joo, Hyung Joon; Park, Chi Yeon; Choi, Seung Cheol; Jeong, Han Saem; Hong, Soon Jun.

In: Molecular Medicine, Vol. 25, No. 1, 33, 15.07.2019.

Research output: Contribution to journalArticle

Kim, Jong Ho ; Lim, I. Rang ; Joo, Hyung Joon ; Park, Chi Yeon ; Choi, Seung Cheol ; Jeong, Han Saem ; Hong, Soon Jun. / Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein e knockout mice. In: Molecular Medicine. 2019 ; Vol. 25, No. 1.
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abstract = "Background: The beneficial effects of angiotensin II type 1 receptor blockers (ARBs) on atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan on reducing neointimal formation and systemic inflammation after carotid artery (CA) injury in Apolipoprotein E knockout (ApoE KO) mice. Methods: ApoE KO mice were randomly allocated to Group I (without CA injury), Group II (without CA injury + Fimasartan), Group III (CA injury), and Group IV (CA injury + Fimasartan). Fimasartan was orally administered everyday starting 3 days before iatrogenic left CA injury. Results: At 28 days, neointimal hyperplasia and the inflammatory cytokines including TNFα, IL-6, ICAM, and MMP-9 in the peripheral blood were significantly reduced in Groups II and IV compared to Groups I and III, respectively. All fimasartan-administered groups revealed significant increases of CD4+CD25+Foxp3+ regulatory T (Treg) cells with increased plasma levels of IL-10 and TGFβ. In addition, increased CD8+ T cells by fimasartan were correlated with reduced smooth muscle cell (SMC) proliferation in the neointima in Groups II and IV. Furthermore, the populations of Treg and CD8+ T cells in total splenocytes were increased in Groups II and IV compared to Groups I and III, respectively. The enlargement of spleens due to CA injury in the Group III was attenuated by fimasartan, as shown in the Group IV. These data indicate that fimasartan significantly reduced SMC proliferation in neointima and increased Treg cells in ApoE KO CA injury mice. Conclusions: This study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation.",
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AU - Kim, Jong Ho

AU - Lim, I. Rang

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AU - Choi, Seung Cheol

AU - Jeong, Han Saem

AU - Hong, Soon Jun

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AB - Background: The beneficial effects of angiotensin II type 1 receptor blockers (ARBs) on atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan on reducing neointimal formation and systemic inflammation after carotid artery (CA) injury in Apolipoprotein E knockout (ApoE KO) mice. Methods: ApoE KO mice were randomly allocated to Group I (without CA injury), Group II (without CA injury + Fimasartan), Group III (CA injury), and Group IV (CA injury + Fimasartan). Fimasartan was orally administered everyday starting 3 days before iatrogenic left CA injury. Results: At 28 days, neointimal hyperplasia and the inflammatory cytokines including TNFα, IL-6, ICAM, and MMP-9 in the peripheral blood were significantly reduced in Groups II and IV compared to Groups I and III, respectively. All fimasartan-administered groups revealed significant increases of CD4+CD25+Foxp3+ regulatory T (Treg) cells with increased plasma levels of IL-10 and TGFβ. In addition, increased CD8+ T cells by fimasartan were correlated with reduced smooth muscle cell (SMC) proliferation in the neointima in Groups II and IV. Furthermore, the populations of Treg and CD8+ T cells in total splenocytes were increased in Groups II and IV compared to Groups I and III, respectively. The enlargement of spleens due to CA injury in the Group III was attenuated by fimasartan, as shown in the Group IV. These data indicate that fimasartan significantly reduced SMC proliferation in neointima and increased Treg cells in ApoE KO CA injury mice. Conclusions: This study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation.

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KW - Neointimal hyperplasia

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