PhD ceremony Mr. R.V. Stan: Endothelial subcellular structures in vascular permeability

PhD ceremony: Mr. R.V. Stan, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Endothelial subcellular structures in vascular permeability

Promotor(s): prof. G. Molema

Faculty: Medical Sciences

Vascular permeability is a cardiovascular function by which endothelial cells lining the blood vessels control the exchange of molecules between blood plasma and the interstitial fluid of different organs. Maintenance of proper vascular permeability is of utmost importance for whole organism physiology and organ function enabling nutrient delivery, waste removal and communication between organ systems. The precise molecular mechanisms controlling vascular permeability continue to elude us. Endothelial subcellular structures/organelles such as caveolae, fenestrae and transendothelial channels have been implicated in permeability over years of research. Little was known as to their molecular composition, regulation and precise function. In this thesis, we describe our work focused on insolating and characterizing the composition of caveolae, fenestrae and transendothelial channels in order to find specific molecular components, which in turn could serve as molecular targets for determining the precise function for these organelles. Our work led to the discovery and cloning of Plasmalemma Vesicle Associated Protein (Plvap/PV1). It is the first identified component of the diaphragms of caveolae, fenestrae and transendothelial channels. We further demonstrated Plvap to be a structural component of the endothelial diaphragms of caveolae, fenestrae and transendothelial channels as well as demonstrated the critical role of the fenestrae diaphragms in maintenance of basal permeability. In summary, our work opens new avenues of research into the structure, components and function of endothelial subcellular organelles involved in permeability and provides new evidence demonstrating the maintenance of vascular permeability as a critical mammalian function necessary for survival.