Regulation of telomerase in endothelial cells in vitro and in vivo

• Applicant: Professorin Dr. Judith Haendeler
• Subject Area: Cardiology, Angiology
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201945599

Telomerase with its catalytic subunit Telomerase Reverse Transcriptase (TERT) has non-telomeric functions besides its telomere-retaining property. TERT is regulated post-translationally, amongst others, by phosphorylation, translocation and degradation. Influences reducing TERT levels in endothelial cells lead to increased apoptosis and a decrease in mitochondrial function and cell migration. Recent epidemiologic studies show that air pollution and as a major constituent carbon black particles promote the occurrence and progression of cardiovascular diseases. In addition, it was demonstrated that particles reduce endothelial function. However, up to now the molecular mechanisms of action of particle concentrations, which we are exposed to permanently, on the vessels have not been identified. Our preliminary data show that non-toxic concentrations of ultrafine carbon black particles reduce telomerase activity. Therefore, the first aim of this project is to elucidate how non-toxic doses of these particles influence TERT and its regulators identified in the previous funding period (Akt, Src/Yes, Shp-2, eNOS) in endothelial cells. In the second aim we will investigate these mechanisms in mice, including TERT-deficient animals. Furthermore, we will specifically investigate the role of carbon black particles on endothelial function in vivo and on myocardial infarction and therein the role of TERT using TERT-deficient mice.

• DFG Programme: Research Grants