PCBs alter gene expression of nuclear transcription factors and other heart-specific genes in cultures of primary cardiomyocytes: possible implications for cardiotoxicity.

1. Polychlorinated biphenyls (PCBs) are well-known environmental pollutants that bioaccumulate mainly in the fatty tissue of animals and humans. Although contamination occurs primarily via the food chain, waste combustion leads to airborne PCBs. From epidemiological studies, there is substantial evidence that cardiovascular disease is linked to air pollution, but little is known about the underlying molecular events. 2. We investigated the effects of Aroclor 1254, a complex mixture of >80 PCB isomers and congeners, on the expression of nuclear transcription factors (GATA-4, Nkx-2.5, MEF-2c, OCT-1) and of downstream target genes (atrial and brain natriuretic peptide, alpha- and beta-myosin heavy chain, alpha-cardiac and alpha-skeletal actin), which play an important role in cardiac biology. 3. We treated cultures of primary cardiomyocytes of adult rats with Aroclor 1254 (10.0 micro M) and found significant induction of the transcription factor genes GATA-4 and MEF-2c and of genes regulated by these factors, i.e. atrial natriuretic peptide, brain-type natriuretic peptide, alpha- and beta-myosin heavy chain, and skeletal alpha actin. 4. We have shown PCBs to modulate expression of genes coding for programmes of cellular differentiation and stress (e.g. atrial natriuretic peptide, brain-type natriuretic peptide) and these alterations may be important in the increase of cardiovascular disease in polluted areas.