Cardiovascular Diseases Major processes discovered behind vascular aging

Cardiovascular Diseases: This is how blood vessels age

Cardiovascular diseases are among the leading causes of death in the Western world. Researchers have now taken a closer look at the molecular processes involved in such diseases based on a specific hereditary disease. Their results could also help understand natural cardiovascular aging processes.

One of the most common causes of death

Cardiovascular diseases lead to arteriosclerosis (arteriosclerosis) and heart failure and are among the leading causes of death in modern industrialized countries. Researchers from Austria have now been able to decipher the molecular mechanisms in cardiovascular diseases as part of the hereditary disease Hutchison-Gilford syndrome (Progerie). Their findings were published in the journal The Journal of Clinical Investigation (JCI).

Cardiovascular diseases are among the leading causes of death in Germany. Researchers have now been able to decipher the molecular processes involved in such diseases. (Image: Kzenon / fotolia.com)

Constant mechanical loads

Cardiovascular diseases such as stroke or heart attack are among the leading causes of death in Western countries.

As the Medical University (MedUni) Vienna writes in a statement, the exact molecular mechanisms in cardiovascular diseases are still unclear.

However, endothelial dysfunction is known to be the beginning of these diseases.

The endothelium is a cell layer that lines the inner walls of blood vessels. These cells are constantly exposed to mechanical stress due to the blood flow.

In healthy cells, a network of cells called the lamina and the cytoskeleton support the cell, helping to maintain its stability and firmness. As a result, changing mechanical loads can be cushioned by the blood pressure.

Strains of blood flow

Scientists from the University of Vienna, the MedUni Vienna, the Ludwig Boltzmann Cluster for Cardiovascular Research and the Boku Vienna have now described for the first time how this cellular framework is impaired in progeria model organisms.

This causes abnormal mechanical reactions in the cell, thereby excessively forming connective tissue in the blood vessels.

"The accumulation of disease-causing mutant proteins in endothelial cells makes the lamina stiff and static, causing high levels of mechanical stress that prevent the endothelium from responding properly to changing blood flow loads," says lead author Selma Osmanagic-Myers.

"This in turn activates cellular signaling pathways that cause fibrosis, vascular hardening and cardiovascular hyperfunction."

Extremely fast aging due to genetic defect

The results are based on studies in Progerie model organisms. This hereditary genetic disease became known to a wider public when 17-year-old Hayley Okines from England died.

The girl suffered from prograny and was an "old woman" at an early age.

The disease is said to have inspired the creators of the film "The Strange Case of Benjamin Button". In it, Brad Pitt is born an old man and is getting younger and younger.

Hope for new therapies

Cardiovascular disease is the most common and life-threatening symptom of the disease. They are caused by mutations in the gene LMNA that lead to the production of a mutant lamina called progerin.

Research group leader Roland Foisner is therefore optimistic: "A better understanding of the molecular defects that lead to cardiovascular disease in Progerie will help to develop new therapies that will improve the lives of patients and prevent early death from cardiac arrest."

And further: "While most recent studies have found defects in the blood vessel muscle cells in progeria, we show that endothelial dysfunction contributes to fibrosis and heart problems," said the scientist.

Bruno Podesser, cardiologist at the Medical University of Vienna, adds: "Interestingly, the Progerie-causing lamin often found in normal aged organisms, but in lower concentrations."

Therefore, the cardiovascular diseases of "normal aged" persons are similar to those of Progerie patients.

"The study therefore provides insight into the underlying molecular mechanisms associated with the erroneous response to mechanical stress due to blood flow as it occurs on curvatures of aged arteries," says Podesser.

Therefore, the study provides an explanation for cardiovascular diseases in progeria at the molecular level and could also help to explain the processes of normal aging of the blood vessels. (Ad)