Exercise attenuates inflammation and limits scar thinning after myocardial infarction in mice

Am J Physiol Heart Circ Physiol. 2015 Jul 15;309(2):H345-59. doi: 10.1152/ajpheart.00683.2014. Epub 2015 May 22.

Abstract

Although exercise mediates beneficial effects in patients after myocardial infarction (MI), the underlying mechanisms as well as the question of whether an early start of exercise after MI is safe or even beneficial are incompletely resolved. The present study analyzed the effects of exercise before and reinitiated early after MI on cardiac remodeling and function. Male C57BL/6N mice were housed sedentary or with the opportunity to voluntarily exercise for 6 wk before MI induction (ligation of the left anterior descending coronary artery) or sham operation. After a 5-day exercise-free phase after MI, mice were allowed to reexercise for another 4 wk. Exercise before MI induced adaptive hypertrophy with moderate increases in heart weight, cardiomyocyte diameter, and left ventricular (LV) end-diastolic volume, but without fibrosis. In sedentary mice, MI induced eccentric LV hypertrophy with massive fibrosis but maintained systolic LV function. While in exercised mice gross LV end-diastolic volumes and systolic function did not differ from sedentary mice after MI, LV collagen content and thinning of the infarcted area were reduced. This was associated with ameliorated activation of inflammation, mediated by TNF-α, IL-1β, and IL-6, as well as reduced activation of matrix metalloproteinase 9. In contrast, no differences in the activation patterns of various MAPKs or adenosine receptor expressions were observed 5 wk after MI in sedentary or exercised mice. In conclusion, continuous exercise training before and with an early reonset after MI ameliorates adverse LV remodeling by attenuating inflammation, fibrosis, and scar thinning. Therefore, an early reonset of exercise after MI can be encouraged.

Keywords: exercise; fibrosis; magnetic resonance imaging; myocardial infarction; remodeling; scar thinning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Cicatrix / physiopathology
  • Cicatrix / therapy*
  • Collagen / metabolism
  • Disease Models, Animal
  • Exercise Therapy*
  • Fibrosis
  • Gene Expression Regulation
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / physiopathology
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, Inbred C57BL
  • Myocardial Contraction
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • RNA, Messenger / metabolism
  • Stroke Volume
  • Time Factors
  • Ventricular Function, Left*
  • Ventricular Remodeling*

Substances

  • Inflammation Mediators
  • RNA, Messenger
  • Collagen
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse