Abstract
Life expectancy keeps increasing in developed countries. Because age is an important independent risk factor for cardiovascular disease (CVD), its impact on healthcare systems is substantial. Aging is accompanied by impaired autophagy, which triggers a strong interest in this highly conserved intracellular recycling process in various disease areas including CVD. We previously reported that impaired autophagy in vascular smooth muscle cells affects vasomotor function and accelerates the development of atherosclerotic plaques. However, the role of endothelial autophagy in vascular disease remains poorly understood, despite numerous studies indicating that endothelial autophagy maintains normal vessel wall biology. In this project, we would like to study in more depth the role and significance of endothelial autophagy in vascular disease by using an appropriate mouse model for defective autophagy in endothelial cells (ECs). Special attention will be given to how endothelial autophagy influences vascular reactivity, arterial stiffness, blood pressure and atherogenesis. A second aim is the prevention of vascular disease by stimulating autophagy selectively in ECs by using a key autophagy inducer linked to an EC-specific homing peptide, thereby avoiding systemic side effects. The knowledge acquired within this project will allow a significant advance in the general understanding of autophagy (and its impaired function) in vascular disease.
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