Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries

J. M. Pyles, K. L. March, M. Franklin, K. Mehdi, R. L. Wilensky, L. P. Adam

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Vascular restenosis involves contraction, proliferation, and remodeling of the arterial wall in response to overstretch injury. Mitogen-activated protein kinases (MAPKs) are implicated in both contraction and proliferation of vascular smooth muscle (VSM), and studies of porcine carotid arterial muscle strips have shown that mechanical stretch leads to the activation of the extracellular signal-regulated kinase (ERK) family of MAPKs in vivo. We, therefore, analyzed the acute effect of mechanical overstretch injury on ERK- MAPK (herein referred to simply as MAPK) activity in porcine coronary and carotid arteries in vivo. Balloon angioplasty catheters were inflated to 6 atm three times over 5 minutes at a balloon-artery ratio of 1.2:1 in either porcine coronary or carotid arteries. The arteries were snap-frozen after angioplasty, and MAPK activity was measured. Angioplasty of the left anterior descending (LAD, n=5), left circumflex (LCx, n=5), and carotid (n=5) arteries effected an increase in MAPK activity compared with the activity in uninstrumented right coronary arteries (RCAs) or carotid arteries from the same animals used for controls. Balloon angioplasty of carotid arteries led to an increase in MAPK activity that was 7.7-fold over the activity in control arteries and comparable to the activity in stretched carotid arterial muscle strips in vivo. The increase in coronary artery kinase activity on angioplasty was variable from animal to animal. The increase in MAPK activity over that in control arteries ranged from 4.5- to 31.7-fold (mean±SEM, 10.7±5.3) in the LAD and 1.8- to 31.3-fold (mean±SEM, 9.7±5.7) in the LCx. There were no apparent inherent differences in the levels of MAPK activity in the three different types of coronary arteries (RCA, LAD, and LCx) without instrumentation. MAPK activation occurs rapidly during angioplasty, suggesting that this kinase may play an early role in initiating the injury response in both porcine coronary and carotid arteries. MAPKs may be key enzymes targeted to treat or prevent restenosis.

Original languageEnglish (US)
Pages (from-to)904-910
Number of pages7
JournalCirculation research
Volume81
Issue number6
DOIs
StatePublished - Jan 1 1997

Keywords

  • Angioplasty
  • Mitogen-activated protein kinase
  • Restenosis
  • Smooth muscle
  • Stretch

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Pyles, J. M., March, K. L., Franklin, M., Mehdi, K., Wilensky, R. L., & Adam, L. P. (1997). Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries. Circulation research, 81(6), 904-910. https://doi.org/10.1161/01.RES.81.6.904