Superfund Research Program
Superfund Chemicals, Nutrition, and Multi-Organ Cardiovascular Risk
Final Progress Reports
From epidemiological studies, there is substantial evidence that cardiovascular diseases are linked to environmental pollution. Dysfunction of endothelial cells is a critical underlying cause of the initiation of many vascular diseases, including cardiovascular diseases such as atherosclerosis. The team’s data so far successfully validated the current hypotheses that were proposed. Some of the major findings include: 1) Coplanar PCBs induce prooxidative and proinflammatory signaling pathways that are critical players in the pathology of atherosclerosis. 2) The cellular lipid milieu clearly modifies the cytotoxicity of PCBs, i.e., linoleic acid and metabolites like leukotoxins interact with PCBs to exacerbate an inflammatory response. 3) Diet-derived antioxidant nutrients or bioactive compounds, such as vitamin E or phenolics, block endothelial activation mediated by PCBs and/or selected lipids. Using LDL-R-deficient mice, which mimic human atherosclerosis, the investigators recently discovered that the type of fat is critical in modifying PCB-induced atherogenic parameters. Indeed, immunohistochemistry data from this in vivo study demonstrated the cumulative effect of corn oil and PCB 77 on aortic VCAM-1 expression. While olive oil-fed mice did not show expression of this adhesion molecule unless animals were injected with PCBs, corn oil feeding alone already resulted in a strong staining for VCAM-1. In corn oil-fed mice injected with PCBs, VCAM-1 expression could even be detected in the subendothelial space, suggesting a progressed state of atherosclerosis with adhesion molecule expression on smooth muscle cells. These data are in agreement with epidemiological studies that suggest that diets high in olive oil or oleic acid protect against cardiovascular diseases. The team’s recent in vivo study with an atherogenic mouse model demonstrates an interaction of PCBs with dietary fat and subsequent changes in lipid metabolism and induction of inflammatory genes. These findings provide clear evidence of the interactive mechanisms of dietary fats and environmental contaminants as mediators of vascular endothelial cell dysfunction and vascular pathologies such as atherosclerosis.
The team's discovery that dietary fats, especially oils rich in omega-6 fatty acids which are common in the American diet, amplify the PCB-mediated endothelial cell dysfunction, and that Mediterranean type diets rich in olive oil, vitamin E and dietary flavonoids, reduce or protect the PCB-induced inflammatory response and associated pathology of blood vessel cells, may be especially relevant for populations near sites of excessive exposure to environmental pollutants such as PCBs.