Related Experiment Video
Updated: Jun 30, 2026
Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure
Published on: December 2, 2014
Cigarette smoke-induced left ventricular remodelling is associated with activation of mitogen-activated protein
Lianzhi Gu1, Vikas Pandey, David L Geenen
1Department of Medical-Surgical Nursing, University of Illinois at Chicago, Chicago, United States.
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.
Insights
Cigarette smoke exposure in rats increased norepinephrine levels and activated specific MAPKs, leading to left ventricular remodeling and systolic dysfunction.
Area of Science:
- Cardiovascular Physiology
- Toxicology
- Molecular Biology
Background:
- Cigarette smoke (CS) is a major risk factor for cardiovascular diseases.
- The molecular mechanisms underlying CS-induced cardiac dysfunction remain incompletely understood.
- Mitogen-activated protein kinases (MAPKs) are key signaling molecules involved in cellular stress responses.
Purpose of the Study:
- To investigate the impact of CS exposure on MAPK activation (ERK1/2, p38, JNK).
- To assess changes in norepinephrine (NE) levels.
- To evaluate alterations in myocardial structure and function.
Main Methods:
- Rats were exposed to cigarette smoke or room air for 5 weeks.
- Echocardiography and pulse-wave Doppler were used to assess cardiac function.
- Western blot analysis was performed to measure MAPK expression and activation.
Main Results:
- CS exposure significantly increased urinary norepinephrine levels.
- Ventricular dimensions were larger, and systolic function was impaired in CS-exposed rats.
- Phosphorylation of p38 and ERK1/2 MAPKs was significantly increased in CS-exposed hearts.
Conclusions:
- Elevated norepinephrine levels and activated MAPKs (p38, ERK1/2) are associated with cigarette smoke-induced left ventricular remodeling.
- These molecular changes may contribute to the observed cardiac dysfunction.
