Cytokine response to diet and exercise affects atheromatous matrix metalloproteinase-2/9 activity in mice

Soo Min Shon, Hee Jeong Jang, Dawid Schellingerhout, Jeong Yeon Kim, Wi Sun Ryu, Su Kyoung Lee, Jiwon Kim, Jin Yong Park, Ji Hye Oh, Jeong Wook Kang, Kang Hoon Je, Jung E. Park, Kwangmeyung Kim, Ick Chan Kwon, Juneyoung Lee, Matthias Nahrendorf, Jong Ho Park, Dong Eog Kim

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)1528-1536
Number of pages9
JournalCirculation Journal
Issue number10
StatePublished - 2017

Bibliographical note

Funding Information:
This work was supported by Global Research Lab (GRL) program (NRF-2015K1A1A2028228) of the National Research Foundation, funded by the Korean government and the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (HI12C1847, HI12C0066).

Publisher Copyright:
© 2017, Japanese Circulation Society. All rights reserved.


  • Atheroma
  • Atherosclerosis
  • Cytokine
  • Matrix metalloproteinase
  • Molecular imaging


Dive into the research topics of 'Cytokine response to diet and exercise affects atheromatous matrix metalloproteinase-2/9 activity in mice'. Together they form a unique fingerprint.

Cite this