Stress and vascular risk -- Elucidating the associations between endothelial dysfunction, telomerase activity, increased susceptibility of the brain to injury and hyperactivity of the neuroendocrine stress axis

• Applicant: Professorin Dr. Karen Gertz, since 7/2017
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Biological Psychiatry
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 266306077

Affective disorders and psychosocial stress confer an increased risk for vascular events such as myocardial infarction or stroke. They also result in increased morbidity and mortality as well as in worse functional outcome after an ischemic lesion. Here, the effects of stress on the vascular system will be investigated in two murine stress models (chronic stress and maternal-deprivation paradigms). In previous studies, we were able to show that chronic stress exacerbates the ischemic damage in a well-characterized vascular lesion model (i.e., stroke). The central hypothesis of this proposal is that chronic stress results in endothelial dysfunction, which in turn bestows a special vulnerability to vascular events. We speculate that altered telomerase activity may be an important underlying molecular mechanism, leading to downstream changes in DNA damage response pathways, increased apoptosis and a limited ability of the endothelium to proliferate in response to an ischemic stimulus. We will study dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis as a potentially crucial mediator of the effects of stress on the endothelium. Finally, to gain further mechanistic insight, we will use lentiviral gene transfer to modulate the expression of the protein component of the telomerase enzyme (TERT) specifically in endothelial cells.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Golo D. Kronenberg, until 7/2017