Effects of exercise training and detraining on atheromatous matrix metalloproteinase activity in mice

Jiwon Kim, Hee Jeong Jang, Dawid Schellingerhout, Jeong Wook Kang, Seungbum Choi, Hyerin Oh, Eo Jin Kim, Su Kyoung Lee, Ji Sung Lee, Ick Chan Kwon, Kwangmeyung Kim, Young Jun Koh, Wi Sun Ryu, Dong Eog Kim

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background and aims: Exercise training (ET) helps treat atherosclerosis. However, many patients stop regular ET for various reasons. The effect of detraining on atherosclerosis is not well studied. We examined the effects of ET vs. short-term detraining on atheromatous matrix-metalloproteinase (MMP) activity in preexisting plaque and circulating cytokines/lipids. Methods and results: Eighteen-week-old apolipoprotein-E−/− mice (n = 56) on a Western diet underwent: 1) ET for 6-weeks (ET5+1), 2) ET for 5-weeks and detraining for 1-week (ET5+0), 3) ET for the last 1-week (ET0+1), or 4) no treadmill ET at all for 6-weeks (ET0+0). Atheromatous MMP-activity was visualized using molecular imaging with an MMP-2/9-activatable near-infrared-fluorescent probe. Compared with no ET (ET0+0), regular ET (ET5+1) decreased carotid atheromatous MMP activity, but this protective effect was significantly blunted by short-term detraining (ET5+0). Short-term detraining after longer-term ET showed a reduction in MMP-activity similar to short-term ET (ET0+1). Blood levels of lipids and cytokines paralleled the molecular imaging results: exercise caused higher levels of high-density lipoprotein, adiponectin, and interleukin-10 and lower levels of vascular cell adhesion molecule, monocyte chemoattractant protein-1, interleukin-1β, and low-density lipoprotein. However, this beneficial effect was short-lived, with the ET5+0 group being similar to the ET0+0 group, and the ET0+1 group being similar to the ET5+1 group. The effect of exercise can be modeled with an exponential-decay of the protective factor of about 15%/day. Conclusions: Even short-term detraining reduces atheroprotective effects, and tips the balance towards atherosclerosis. This suggests that ET, to be effective, needs to be prolonged and regular, and that detraining should be avoided.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
StatePublished - Apr 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier B.V.


  • Atherosclerosis
  • Cytokines
  • Exercise training
  • Matrix metalloproteinase
  • Molecular imaging


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