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Cigarette smoke‐induced left ventricular remodelling is associated with activation of mitogen‐activated protein kinases
Author(s) -
Gu Lianzhi,
Pandey Vikas,
Geenen David L.,
Chowdhury Shamim A.K.,
Piano Mariann R.
Publication year - 2008
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2008.08.009
Subject(s) - medicine , kinase , p38 mitogen activated protein kinases , mapk/erk pathway , western blot , protein kinase a , phosphorylation , cardiology , endocrinology , chemistry , biochemistry , gene
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 NH 2 ‐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.