Organ- och kärltypsspecifikt bildande av lymfatisk vaskulatur: implikationer för kärl funktion och sjukdom

Tidsperiod: 2014-01-01 till 2019-12-31

Projektledare: Taija Makinen, Taija Mäkinen

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 18 000 000 SEK

Lymphatic system is composed of a hierarchy of vessels with specific features serving their unique functions: lymphatic capillaries that absorb interstitial fluid and collecting lymphatic vessels that transport lymph to the cardiovascular system. Failure of lymphatic vessels can lead to lymphoedema and contribute to pathogenesis of obesity, atherosclerosis and cardiovascular disease. Notably, pathological lymphatic diseases mostly affect vessels of a specific type and tissue. I hypothesise that organ- and vessel-type specific manifestation of lymphatic dysfunction is due to vascular bed-specific differences in the origin and mechanism of vessel formation. In this project my aim is to identify genes and mechanisms regulating the development of specific lymphatic vascular beds and their origin in mice and humans. Towards this aim, we will determine genetic signatures of capillary and collecting vessel endothelial cells from different organs by microarray analysis. Mutant mice with organ-specific lymphatic defects will be analysed and the origin of the vasculature will be studied by genetic lineage tracing. We will also identify and functionally characterise novel disease mutations in human lymphoedema with capillary or collecting vessel dysfunction by whole-exome sequencing and generation of mouse models. This work is expected to bring fundamental novel understanding of vascular bed-specific requirements for lymphatic development and disease processes in lymphatic disorders.