Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein kinases.
OBJECTIVE
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.
Gu
Lianzhi
L
Department of Medical-Surgical Nursing, University of Illinois at Chicago, Chicago, United States.
Pandey
Vikas
V
Geenen
David L
DL
Chowdhury
Shamim A K
SA
Piano
Mariann R
MR
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004452:Echocardiography; D004789:Enzyme Activation / Q000187:drug effects; D006352:Heart Ventricles / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D014028:Tobacco Smoke Pollution; D020928:Mitogen-Activated Protein Kinases