The sequence of biological events that permits an organism to maintain tissue viability in hypoxia remains poorly understood. Variations in oxygen concentration lead to respiratory, metabolic and vascular adaptations in tissues. How hypoxic endothelial cells (EC) integrate chemical signals with mechanical cues from their local tissue microenvironment in order to produce functional capillary networks that exhibit specialized form remains an open question. A key role of hypoxia in the regulation of many endothelial functions is nevertheless well established and growing evidence show that angiogenesis, defined as the events leading to blood vessels formation by sprouting or growth of preexisting vessels, can be triggered by hypoxia, both during development and in pathological conditions, such as cardiovascular ischemia and tumors. Our team is interested in understanding how angiogenesis and vascular integrity are regulated in hypoxic conditions.
We are using a multidisciplinary approach combining gene discovery approach for complex human diseases, vascular cell biology (endothelial and smooth muscle cells) cell cultures in 2-D and 3-D, biochemistry, molecular biology, various imaging approaches (confocal analyses, videomicroscopy), gene expression analyses, protein production, and preclinical models of human diseases. Our efforts have recently been focused on characterizing the role of Thrombospondin-1, Angiopoietin-like 4 and Lysysl Oxidase like 2 in regulating angiogenesis and vascular integrity.
