Cigarette Smoke-Induced Left Ventricular Remodelling Is Associated With Activation of Mitogen-Activated Protein Kinases

Eur J Heart Fail. 2008 Nov;10(11):1057-64. doi: 10.1016/j.ejheart.2008.08.009. Epub 2008 Sep 24.


Aim: To determine the effects of cigarette smoke (CS) exposure on the expression/activation of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK1/2], p38-kinase [p38] and c-Jun NH2-terminal protein kinase [JNK]), norepinephrine (NE) levels and myocardial structure and function.

Methods: Rats were randomised to two groups: CS-exposed (n=12) or room air (CON) (n=10). After 5 weeks, the animals underwent echocardiography with pulse-wave Doppler flow measurements. Hearts were removed for microscopy and Western blot analysis.

Results: CS exposure was associated with significant increases in NE urinary levels and larger ventricular dimensions (mm) (CON=left ventricular end diastolic dimension [LVEDD] 7.99+/-0.10, LV end systolic dimension [LVESD] 4.55+/-0.20, CS=LVEDD 8.3+/-0.10, LVESD 5.3+/-0.09, p=0.026, p=0.003). There was also evidence of systolic dysfunction in the CS-exposed group compared to the CON group (fractional shortening %, CON=43+/-2, CS=36+/-.09, p=0.010). In CS-exposed hearts, significant increases in phosphorylated p38/total p38 (0.975+/-0.05) and phosphorylated ERK1/2/totalERK1/2 (1.919+/-0.050) were found compared to CON hearts (0.464+/-0.008, 0.459+/-0.050, respectively). No significant differences were found in JNK levels between the groups.

Conclusions: Increased NE levels and MAPK activation are associated with CS-related left ventricular remodelling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Echocardiography
  • Enzyme Activation / drug effects
  • Heart Ventricles / enzymology*
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Male
  • Microscopy, Electron
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Myocardium / enzymology
  • Myocardium / ultrastructure
  • Radioimmunoassay
  • Rats
  • Rats, Sprague-Dawley
  • Smoking / adverse effects*
  • Tobacco Smoke Pollution / adverse effects*
  • Ventricular Remodeling / drug effects*


  • Tobacco Smoke Pollution
  • Mitogen-Activated Protein Kinases