The formation of blood vessels or angiogenesis is a complex process. This process involves multiple mechanisms of inhibition and stimulation that activate simultaneously, “like the cogs in a wheel”. Certain cells in blood vessels, called endothelial cells, play a key role in this process, regulating the exchange between blood and tissues, says lead author Prof. Ralf Benndorf, a pharmacologist at MLU’s Institute of Pharmacy. .
Targeting a “haemostasis” protein
Here, the research is focusing on a protein important for hemostasis: the thromboxane A2 receptor (a cytokine) which causes platelets to adhere and contributes to the constriction of blood vessels. It was known that patients with cardiovascular disease and pathological abnormalities of blood vessels have increased levels of these receptor proteins in their blood vessels, but the link between these increased levels and the development of cardiovascular disease was unknown.
The study: By deciphering a complex interaction triggered by this receptor protein, the team observes that the development of the disease begins with excessively high levels of the protein in the blood vessels:
- the receptor protein triggers the production of the pro-inflammatory enzyme cyclooxygenase-2;
- this enzyme in turn produces messenger substances that activate the receptor;
- this cycle of reinforced activation of the receptor in the cells of the blood vessels causes the cells to find it difficult to form new blood vessels;
- this activation also considerably restricts the function of the endothelial cells: the researchers observe, by microscopy, that the higher the density of receptors, the more the cells are “tense”.
Why more thromboxane A2 receptor in blood vessels people with cardiovascular disease? At this stage, scientists do not know how to answer. However, as of now, the receptor appears as a promising biomarker in addition to being a promising pharmacological target.
A new therapeutic option to fight cardiovascular disease? Receptor inhibition could represent a new treatment option for patients who have elevated levels of the thromboxane A2 receptor in their blood vessels. This treatment could indeed improve vascular function and regeneration.
Already some first tests: the first drugs targeting the protein are already being tested for use in other applications. Although these molecules have not yet been approved, the preliminary results of in vitro and animal trials indicate good tolerance and an ability to improve vascular function. A preclinical study should follow, in the animal model of cardiovascular diseases,
before proceeding to clinical trials in humans.