Cigarette
smoke is a major risk factor for
cardiovascular diseases. It contains thousands of compounds that activate the
aryl hydrocarbon receptor (AhR). In addition,
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD), the most potent AhR
ligand, has been shown to cause cardiotoxic effects in several in vivo models. Although induction of
CYP1 family is the most important effect of AhR activation, the role of CYP1 induction in mediating the cardiotoxic effect of
TCDD is usually overlooked. Therefore, we investigated whether AhR activation causes a hypertrophic effect in H9c2 cells and we related this effect to changes in CYP gene expression. In the current study, the cardiac derived H9c2 cells were treated with two AhR
ligands,
TCDD and
beta-naphthoflavone (BNF), for 24 and 48h. The expression of the hypertrophic markers,
atrial natriuretic peptide (
ANP) and
brain natriuretic peptide (BNP), and several CYP genes were measured by real-time PCR. Treatment of H9c2 cells with
TCDD or BNF for 24h caused a significant induction of
CYP1A1, CYP1B1, and CYP4A1; however, there was no change in the expression of other genes. On the other hand, treatment of the cells with
TCDD or BNF for 48h caused a significant induction of the hypertrophic markers,
ANP and BNP, and several CYP genes such as
CYP1A1, CYP1B1,
CYP2E1, CYP2J3, and CYP4F4 parallel to a significant increase in the cell surface area. Neither
TCDD nor BNF increased the oxidative stress in H9c2 cells at all concentrations tested. Interestingly,
resveratrol, an AhR antagonist, protected the cells from
TCDD-induced
hypertrophy. In conclusion, AhR
ligands caused a hypertrophic effect in H9c2 cells which was associated with induction of several CYP genes which can be prevented by
resveratrol.