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European Journal of Heart Failure 2008 10(11):1057-1064; doi:10.1016/j.ejheart.2008.08.009
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© 2008 European Society of Cardiology

Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein kinases

Lianzhi Gua, Vikas Pandeya, David L. Geenenb, Shamim A.K. Chowdhuryb and Mariann R. Pianoa,*

a University of Illinois at Chicago, Department of Medical-Surgical Nursing United States
b University of Illinois at Chicago, Department of Medicine, Section of Cardiology and Center for Cardiovascular Research United States

* Corresponding author. University of Illinois at Chicago, 845 S. Damen Ave., Chicago, Illinois 60612, United States. Tel.: +1 312 413 7908; fax: +1312 996 7934. E-mail address: piano{at}uic.edu (M.R. Piano)


  Abstract

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) 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 (fractional shortening %, CON=43±2, CS=36±.09, p=0.010). In CS-exposed hearts, significant increases in phosphorylated p38/total (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. Published by Elsevier B.V. on behalf of European Society of Cardiology.

Key Words: Cigarette smoke • Echocardiography • Ventricular remodelling • Mitogen-activated protein kinases

Received March 6, 2008; Revised June 13, 2008; Accepted August 18, 2008


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