Abstract P324: Unhealthy Diet and Air Pollution Compromise Human Cardiovascular Cell Functions: A First Mechanistic Analysis

Abstract

Diet and pollution are environmental factors known to compromise ″healthy cardiovascular aging″. The molecular consequences of the permanent burden for aging of the cardiovascular system are unknown, since they have never been examined in primary, adult human cells. Therefore, this study investigates the impact of unhealthy diet on aging-related signaling pathways of human, primary cardiovascular cells and of airborne particles on human endothelial cells, as several studies demonstrated that ultrafine particles can enter the circulation and thus may interact with endothelial cells directly. Nutrition health reports have shown that the diet in industrialized countries contains more than 100 mg/dl low density lipoprotein (LDL) and a too high fraction of monosaccharides, especially fructose, which is metabolized insulin-independently. Both components have been shown to increase the risk for cardiovascular diseases. To simulate unhealthy diet we supplemented cell culture media of human, primary endothelial cells (EC), smooth muscle cells (SMC) and cardiomyocytes (CM) with 100 mg/dl LDL and replaced 1/3 of the glucose with fructose for one week. This treatment did not induce cell death in any of the cell types. However, we observed increased senescence, loss of endothelial nitric oxide synthase and increased nuclear localization of Foxo3 in EC, increased proliferation in SMC and hypertrophy in CM. With respect to pollution we have used ultrafine carbon black particles (ufCB), one of the major constituents of industrial and exhaust emissions, in concentrations our vessels are constantly exposed to. These concentrations of ufCB are non-toxic and non-inflammatory for EC. Despite these missing immediate effects, ufCB dramatically reduced the S-NO content, a marker for NO-bioavailability in EC and increased reactive oxgen species formation. As a consequence, ufCB dramatically increased senescence of EC after two weeks. Thus, unhealthy diet and a high burden of ultrafine carbon black nanoparticles, to which we are exposed every day, seem to induce a ″cardiovascular aging″ phenotype and can lead to severe cardiovascular diseases.