Anti-angiogenic and teratological activities associated with exposure to total particulate matter from commercial cigarettes

Angiogenesis and the embryonic movement (EM) pathway are evolutionarily conserved mechanisms, which are essential for embryonic development. Deviation in these processes from exposure to cigarette total particulate matter (TPM) may produce vascular, morphogenetic, and teratological disorders. The anti-angiogenic and teratogenic potential of TPM from commercially available cigarettes was studied. In vitro effects of TPM on angiogenesis were determined with different assays utilizing human umbilical vein endothelial cells (HUVEC). A chicken embryo model was used to demonstrate the in vivo effects of TPM on EM, vascular development, and organogenesis. The current study provides evidence that cigarette TPM plays an impeding role in endothelial cell proliferation, migration, tube formation, and sprouting, which are crucial factors in angiogenesis. Video recordings and kinematic analyses of the TPM exposed chicken embryos revealed a striking decrease in EM. Likewise, exposure of TPM to embryos resulted in ocular, mandibular, and abdominal hemorrhaging. Several teratologies including ectopia cordis, as well as bi-trunked and mammoth headed embryos were frequent findings among TPM treated embryos. These results are strongly reminiscent of morphogenetic and teratogenic deformities in TPM exposed embryos. This shows that cigarette smoking during pregnancy can be fatal to growing embryos. In addition, TPM may produce defective morphogenesis, leading to various pathologies.