|A breakthrough towards preventing and treating cardiovascular diseases
|Pr. Aksam Merched's latest discoveries
The hardening of arteries - also known as 'atherosclerosis' - can cause cardiovascular diseases (CVD),
which can lead to heart attacks and strokes. New evidence has been uncovered strengthening the link
between inflammation - a defensive reaction of the body - and cardiovascular diseases. This could lead to
new innovative preventive and therapeutic strategies, and perhaps ultimately to a cure for atherosclerosis..
According to the study, defects in housekeeping activities
such as removal of cell debris and waste (linked to elevated
levels of lipids in the blood or hyperlipidemia) may
exasperate immune reactions. At some stage these
reactions target the body own components (self) or become
autoreactive. Autoimmune responses to specific vascular
targets may lay the foundations for new atherosclerotic
lesions, and continuous challenges by the immune system
may become the source of continual seeding for the buildup
of a growing, dynamic plaque.
Inflammation is a double-edged sword. It is an important and necessary biological reaction, usually triggered
by the body to ease pain and initiate the healing process. Left unabated, however, it can cause progressive
destruction of tissue, leading to many diseases.
Although the inflammatory aspect of cardiovascular diseases is now well recognised, current knowledge of
the causes of this inflammatory reaction has been somewhat limited. Moreover, the exact nature of internal
vascular stimuli that trigger immune responses has not yet been fully researched. One reason for this deficit
is the lack of an appropriate animal model, which is something the project has addressed.
Several studies have shown that atherosclerotic patients develop a perturbed inflammation in their arteries,
suggesting that autoimmune processes – the failure of an organism to recognise its own constituent parts –
may play a role in the development of atherosclerosis.
Autoimmunity takes the driver seat in the engine of atherogenesis
|Researchers and authors of the report (from left to right)
Merched A, Daret D, Li L, Franzl N, Sauvage-Merched M.
|(Update of a story first reported by the European Commission Research and Innovation website - June 2016)
|Localisation of autoantibodies (red) and
inflammatory cells (magenta) inside an emerging
atheroma (delimited by dashed line). Smooth
muscle cells are stained in green, nuclei in blue.
'Atherosclerosis' is a chronic and slowly progressive pathological condition involving the inflammatory
system. It leads to an accumulation of plaque – containing fatty materials and inflammatory cells – in the
walls of the arteries. Complications from advanced atherosclerosis can cause CVD, leading to a heart attack
or stroke. Every year, CVD causes over millions of deaths worldwide.
The American Heart Association and EU-funded project has opened up the possibility of finding new
effective treatments by developing a genetically modified mouse model that mimics patients with aggressive
inflammatory diseases which display symptoms of atherosclerosis.
“Using the latest tools of molecular biology and proteomics [the study of proteins, which perform important
functions within the body], we have identified molecular targets [for possible future therapies] of the immune
system in the arterial vessel walls,” explains project researcher Aksam Merched. Dr Merched named these
targets as "vascular autoimmunosome". “We were able to come up with some missing puzzle pieces
related to our understanding of how CVD is caused.”
Dr Merched believes that the findings could lead to the development of innovative preventive and therapeutic
approaches, which could ultimately bring a cure for atherosclerosis and help save millions of lives.
“Obviously, clinical validation of these discoveries is a prerequisite to any translational application in
patients,” he says.
How the lesions build up?