CARDIOVASCULAR DISEASE: Targeting a single protein could be the therapeutic key

The formation of blood vessels or angiogenesis is a complex process. This process involves multiple inhibition and stimulation mechanisms that are activated simultaneously, “like the cogs in a wheel”. Certain cells in blood vessels, so-called endothelial cells, play a key role and regulate the exchange between blood and tissue, says lead author Prof. Ralf Benndorf, pharmacologist at the Institute of Pharmacy at MLU.

Targeting a “hemostasis” protein

The research focuses on a protein important for hemostasis: the thromboxane A2 receptor (a cytokine), which causes platelets to stick and helps to constrict blood vessels. It was known that patients with cardiovascular disease and pathological blood vessel abnormalities have elevated levels of these receptor proteins in their blood vessels, but the relationship between these elevated 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 excessive 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 increased activation of the receptor in the cells of the blood vessels makes it difficult for the cells to form new blood vessels;
  • This activation also significantly restricts the function of the endothelial cells: the researchers observe under the microscope that the cells are more “tense” the higher the density of the receptors.

Why more thromboxane A2 receptor in blood vessels People with cardiovascular disease? At this stage, scientists don’t know how to respond. As of now, however, the receptor appears to be a promising biomarker in addition to being a promising pharmacological target.

A new therapy option to fight cardiovascular disease? Inhibiting the receptor could represent a new treatment option for patients with elevated levels of the thromboxane A2 receptor in their blood vessels. This treatment could actually improve vascular function and regeneration.

Some first tests: first drugs targeting the protein are already being tested for other applications. Although these molecules are not yet approved, preliminary results from in vitro and animal studies indicate good tolerability and an ability to improve vascular function. A preclinical study in an animal model of cardiovascular diseases is to follow,

before proceeding with human clinical trials.

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