Endothel and Microcirculation


Organ perfusion is regulated by diameter changes of the smallest arteries (arterioles). The arteriolar diameters are controlled by endothelial cells, which form the innermost cell layer in vessels. The endothelium modulates the activity of the adjacent smooth muscle cell by releasing different dilator and constrictor mediators and thereby exerts its control function on vascular tone and thus blood flow. Endothelial function is studied by means of intravital microscopy in the skeletal muscle of mice, using the isolated perfused heart or isolated vessels but also by telemetric measurement of arterial pressure in conscious animals. The arterioles that provide and control blood flow to the tissues can be directly observed using intravital microscopy. Thus, vascular diameter, blood flow velocity, and the membrane potential of vascular cells (endothelial and smooth muscle cells) can be directly assessed. A topic of special interest is the coordination of vascular cell behaviour along the length of the vessel as vascular cells do not act independently of each other but form a coordinated cellular network. Many vasomotor stimuli do not only elicit a diameter change at the site of localized application but also induce diameter changes at remote upstream sites without stimulating these areas directly. Such remote vascular responses (conducted response) require intercellular connections allowing signals to be transmitted from cell to cell. The molecular bricks of these channels are the connexin proteins which cluster to form so-called gap junctions. Overall, the studies are aimed to examine the role of endothelial mediators and gap junction proteins (connexins) in the control of blood flow to the tissues.

In collaboration with the Department for Integrative and Experimental Genomics, genes that have been demonstrated to be associated with myocardial infarction and coronary disease are examined to identify their functional roles in physiologic and pathophysiologic models. Hitherto, blood pressure measurement, development of atherosclerosis, and thrombus formation are studied in vivo in gene-deficient mice. The studies are aimed to identify how certain genes lead to coronary diseases and provide new ideas for treatment strategies.