Research in the Eichmann group concerns vascular system development and contribution to human pathologies. Endothelial cells (ECs) that constitute the vascular system proliferate and differentiate at the same rate as the organism grows, to ensure oxygen and nutriment supply of tissues and cells. In adults, vascular development becomes quiescent and EC proliferation occurs only in certain physiological situations (wound healing, physical exercise, pregnancy) and pathologies, including diabetes, ageing-associated macular degeneration, tissue ischemia (heart, brain, legs) and malignant tumors.
The long-term goal of the laboratory is to understand the cellular and molecular mechanisms controlling vascular patterning. We aim to identify key molecular events underlying angiogenesis, lymphangiogenesis and arteriogenesis and to establish the principles governing development of the vertebrate vascular system. Vessel networks are vulnerable to diseases, and abnormal vascular development in cardiovascular disease, cancer and diabetes is the major cause of morbidity and mortality in the developed world. We expect that understanding mechanisms controlling developmental vessel patterning will lead to novel strategies to prevent these diseases.
Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.
RATIONALE : Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood.
OBJECTIVE : We set out to identify factors that promote arterial endothelial cell fate in vivo.
METHODS AND RESULTS : We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors.
CONCLUSIONS : These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease.
Circ Res (2016) 119: 607-620More