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Sicyos angulatus ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice.

ABSTRACT: Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE-/-) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE-/- mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor ? (Tnf?) and interleukin-6 (Il-6) were significantly decreased in the aorta of SA administered apoE-/- mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction Tnfa, Il-6 and Il-1? in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE-/- mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE-/- mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis.

SUBMITTER: Kim YH

PROVIDER: S-EPMC5740582 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Sicyos angulatus ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice.

Kim Yong-Hoon YH Noh Jung-Ran JR Hwang Jung Hwan JH Kim Kyoung-Shim KS Choi Dong-Hee DH An Jin-Pyo JP Oh Won-Keun WK Lee Chul-Ho CH

Experimental and therapeutic medicine 20171010 6

Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE-/-) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage duri ...[more]

PMID: 29285134

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Project description:Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE(-/-) mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.

Dataset Information

Sicyos angulatus ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice.

Publications

<i>Sicyos angulatus</i> ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice.

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