Amygdalin ameliorates the progression of atherosclerosis in LDL receptordeficient mice.
Mol Med Rep
; 16(6): 8171-8179, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28983592
ABSTRACT
Previous studies have demonstrated that regulatory T cells (Tregs) are pivotal in the regulation of T cellmediated immune responses in atherosclerosis, a chronic autoimmunelike disease. In the authors' previous studies, it was demonstrated that amygdalin ameliorated atherosclerosis by the regulation of Tregs in apolipoprotein Edeficient (ApoE/) mice. Therefore, the aim of the present study was to investigate the therapeutic effect of amygdalin on lowdensity lipoprotein (LDL) receptor deficient (LDLR/) mice, and to examine its immune regulatory function by the stimulation of Tregs. To establish an atherosclerosis mouse model, the LDLR/ mice were fed a high fat and high cholesterol diet then the total plasma cholesterol, triglyceride, LDL and chemokines levels were measured by an ELISA. Following sacrificing the mice, the upper sections of the aorta were stained by hematoxylin and eosin, and Oil red O to assess the plaque area. Then western blotting and reverse transcription polymerase chain reactions were performed to analysis the expression levels of cluster of differentiation 68, monocyte chemoattractant protein1, matrix metalloproteinase (MMP)2, MMP9 and forkhead box P3 (Foxp3). To further confirm the activation of FOXP3 by amygdalin, lentiviruses carrying Foxp3 shRNA were injected into the mice, and the serum cytokines levels were measured by ELISA. Following feeding of the mice with a highfat/highcholesterol diet, the LDLR/ mice demonstrated comparatively higher levels of triglyceride, total cholesterol and LDL, compared with levels in the amygdalintreated mice. By comparing the vessel area, lumen area, plaque area, and percentage aortic plaque coverage, the effects of amygdalin on preexisting lesions were assessed. In addition, the levels of CD68, monocyte chemoattractant protein1, MMP2 and MMP9 were analyzed, and analysis of the expression of interleukin (IL)1ß, IL6 and tumor necrosis factor (TNF)α indicated that the mice treated with amygdalin had decreased expression of proinflammatory cytokines. The mRNA and protein levels of Foxp3 were also quantified, and the mice treated with amygdalin demonstrated an increased number of Tregs. The knockdown of Foxp3mRNA resulted in the increased secretion of IL1ß, IL6 and TNFα. Therefore, the data indicated that amygdalin regulated the formation of atherosclerosis and stabilized the plaque by suppressing inflammatory responses and promoting the immunemodulation function of Tregs. Taken together, the results demonstrated the therapeutic effect of amygdalin on atherosclerosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Aterosclerose
/
Amigdalina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2017
Tipo de documento:
Article