Cardiovascular diseases: how blood vessels age
Cardiovascular disease is one of 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. Your results could also help you understand natural cardiovascular aging processes.
One of the most common causes of death
Cardiovascular diseases lead to arteriosclerosis (hardening of the arteries) and heart failure and are among the most common causes of death in modern industrialized countries. Researchers from Austria have now succeeded in decoding the molecular mechanisms in cardiovascular diseases in the context of the hereditary disease Hutchison-Gilford syndrome (progeria). Their results have been published in The Journal of Clinical Investigation (JCI).
Constant mechanical loads
Cardiovascular diseases such as a stroke or heart attack are among the leading causes of death in western countries.
As the Medical University (MedUni) Vienna writes in a communication, the exact molecular mechanisms in cardiovascular diseases are still unclear.
However, it is known that malfunctions in the endothelium are at the beginning of these diseases.
The endothelium is a layer of cells that lines the inner walls of blood vessels. These cells are exposed to constant mechanical stress due to the blood flow.
In healthy cells, a network in the cell nucleus called lamina and the cytoskeleton support the cell and help it to maintain stability and strength. As a result, changing mechanical loads caused by blood pressure can be cushioned.
Blood flow pressures
Scientists from the University of Vienna, MedUni Vienna, the Ludwig Boltzmann Cluster for Cardiovascular Research and Boku Vienna have now described for the first time how this cellular framework is affected in progeria model organisms.
This causes abnormal mechanical reactions in the cell, causing excessive connective tissue to form in the blood vessels.
"The accumulation of the disease-causing, mutant proteins in cells of the endothelium make the lamina stiff and static, which causes high mechanical stress that prevents the endothelium from responding correctly to changing stresses in the blood flow," explains lead author Selma Osmanagic-Myers.
"This, in turn, activates cellular signaling pathways that cause fibrosis, hardening of the blood vessels and cardiovascular hyperfunction."
Extremely rapid aging due to genetic defects
The results are based on studies in progeria model organisms. This genetic hereditary disease became known to a wider audience when 17-year-old Hayley Okines from England died.
The girl suffered from progeria and was an "old woman" from an early age.
The disease is also said to have inspired the makers of the film "The Strange Case of Benjamin Button". Brad Pitt is born an old man and is getting younger and younger.
Hope for new therapies
Cardiovascular diseases are the most common and life-threatening symptom of the disease. They are caused by mutations in the LMNA gene that lead to the production of a mutated lamine called progerin.
Research group leader Roland Foisner is therefore optimistic: "A better understanding of the molecular defects that lead to cardiovascular diseases in progeria will help to develop new therapies that improve the living conditions of patients and prevent early death from cardiac arrest."
And further: "While most previous studies have found defects in the muscle cells of the blood vessels in progeria, we show that the malfunction of the endothelium contributes to fibrosis and heart problems," said the scientist.
Bruno Podesser, cardiologist at the Medical University of Vienna, adds: "Interestingly, the laminate that causes progeria is often found in normal aged organisms, but in lower concentrations."
The cardiovascular diseases of “normally aged” people are therefore similar to those of progeria patients.
"The study therefore provides insight into the underlying molecular mechanisms associated with the erroneous response to mechanical stress from blood flow that occurs in curvatures of aged arteries," said Podesser.
Therefore, the study offers 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)