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


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 TNF?, 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 TGF?. 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.

SUBMITTER: Kim JH 

PROVIDER: S-EPMC6632006 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Kim Jong-Ho JH   Lim I-Rang IR   Joo Hyung Joon HJ   Park Chi-Yeon CY   Choi Seung-Cheol SC   Jeong Han Saem HS   Hong Soon Jun SJ   Hong Soon Jun SJ  

Molecular medicine (Cambridge, Mass.) 20190715 1


<h4>Background</h4>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.<h4>Methods</h4>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  ...[more]

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2023-03-09 | GSE220512 | GEO