Blood vessels are extremely dynamic: depending on the external conditions, they can adapt their permeability for nutrients, their contractility, and even their shape. Unlike cardiac muscle cells, for example, the smooth muscle cells in blood vessels demonstrate a high degree of plasticity, so they can specialise or multiply as required, even repairing damage to the vessel wall. This vascular remodelling is evidently precisely regulated. Disruptions are extremely significant in conditions such as atherosclerosis or high blood pressure. At the Max Planck Institute for Heart and Lung Research in Bad Nauheim, scientists conducting research on genetically modified mice have discovered how external signals regulate vascular remodelling at cell level. This has created an entirely new understanding of regulation, which could pave the way for new approaches in the prevention and treatment of atherosclerosis and other vascular diseases.
The walls of blood vessels consist of smooth muscle cells, elastic fibres, and endothelial cells, which line the interior surface of the vessel. The vessels change their permeability and contractility as required. If a blood vessel is damaged, existing smooth muscle cells can give rise to new specialised muscle cells to repair it. However, in the case of a vascular problem, this necessary and useful cell plasticity can have negative consequences. For example, if a coronary blood vessel is opened up with dilatation and stents via a catheter, muscle cell growth may cause it to narrow once again. In the common condition atherosclerosis or vascular calcification, too, remodelling processes lead to formation of the dreaded plaque. All these processes are regulated by hormones or neurotransmitters, some of which are released by cells and nerves in the vessel wall. Most of these vasoactive messengers work by binding to receptors, which in turn, once activated, bind to what are known as G proteins. These are situated on the inside of the cell membrane and relay the signal from there into the cell interior.
"There are two different families of G proteins which play a crucial role in vascular remodelling. They are called Gq/G11 and G12/G13 after their protein components," explains Max Planck scientist Stefan Offermanns, who has been researching these proteins and their molecular signalling pathways for several years now. In the latest study on genetically modified mice, the team was able to demonstrate for the first time how, in a living animal, these two signalling pathways are regulated by messengers. "Contrary to expectations, the two G protein-mediated signalling pathways antagonistically regulate the plasticity of smooth muscle cells," says Offermanns, summarising the findings. This is surprising in that these signalling pathways act together in other contexts: stimuli that promote vessel contraction and thus increase blood pressure activate both signalling pathways in parallel.