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

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. Published by Elsevier B.V. on behalf of European Society of Cardiology.