Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice

Title
Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice
Authors
권익찬김광명손수민장희정Dawid Schellingerhout김정연류위선이수경김지원박진용오지혜강정욱제강훈박정이이준영Matthias Nahrendorf박정호김동억
Keywords
Atheroma; Atherosclerosis; Cytokine; Matrix metalloproteinase; Molecular imaging
Issue Date
2017-10
Publisher
Circulation journal
Citation
VOL 81, NO 10, 1528
Abstract
Background: The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise. Methods and Results: Apolipoprotein-E knock-out (ApoE(-/-)) mice (n= 56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n= 18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. Conclusions: Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.
URI
https://pubs.kist.re.kr/handle/201004/68527
ISSN
1346-9843
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KIST Publication > Article
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