calcification is a condition in which heart fibroblast cells are converted into
osteoblast-like cells, leading to calcification. This makes the heart cells
rigid and affects the flow of blood.
- Researchers have now
identified small molecules that can disrupt the ENPP1 protein and prevent 50%
- A drug etidronate is found to result in 100%
reduction in calcification. This is a preventive drug; scientists are now
trying to identify a drug that could reverse the process of calcification.
Scientists from The
University of California, Los Angeles have discovered that connective tissue in
the heart, in response to injury, turn into bone-producing cells. This
understanding of how the calcium deposits are formed after a person survives
heart damage will aid in devising better strategies for treatment and care. In
the same study, the scientists showed how blocking an enzyme that is involved
in the regulation of bone mineralization could prevent the calcification in the
Calcification of the
bone gives bones its strength and there is rarely calcification outside of the
bones. However, there is calcification of
, organs including
the kidneys and the heart that is found which results in these tissues becoming
rigid. There is a certain amount of calcification that occurs due to advancing
age, however, conditions like diabetes and heart injury which can increase the
calcification process. The calcified heart conducts electrical impulses less
effectively and there is no known treatment for these calcium deposits.
‘Reversal of heart calcification could give a new lease of life to heart cells.’
Arjun Deb from the
University of California's Eli and Edythe Broad Center of Regenerative Medicine
and Stem Cell Research and the senior author of the study said "Heart
calcification has been understudied and underreported. We asked the question,
'What are the cells in the heart that cause calcification?' and given the
strong association between tissue injury, fibrosis, and calcification, we
hypothesized that maybe it is cardiac fibroblasts [cells that give rise to scar
tissue after injury] that are contributing to the calcification
Tagging Fibroblast Cells
Deb and his colleagues
conducted a series of experiments on mice by genetically tagging cardiac
fibroblast cells and studying the effect after heart injury. The researchers
found that the cardiac fibroblasts transformed into osteoblast-like bone
These transformed cells
were then transplanted into heathy mice and were found to result in soft tissue
calcification that was witnessed in the donor mice. These cells also resulted
in tissue calcification when injected into human fibroblast cells on a culture
(Ectonucleotide Pyrophosphatase / Phosphodiesterase 1)
The protein ENPP1 was
found to be released in the cardiac fibroblasts after heart injury.
- 50% reduction in calcium deposition
was observed when the researchers injected several small molecules that
disrupted the function of ENPP1.
- 100% reduction in calcium
deposits was observed when a drug called etidronate was
Deb who holds multiple
posts at the UCLA David Geffen School of Medicine, added "We now want to
see whether this is a common pathway to calcification regardless of etiology
and if what we found can be broadly applied to tissues across the body."
Tissue Calcification of the Heart
calcification of the heart is generally witnessed after heart injury
or due to the natural process of aging. The main problem associated with this
is aortic valve stenosis.
Aortic Valve Stenosis
This condition is
associated with a constriction to the opening of the heart valves. While it
could occur due to a congenital problem, calcification is the prime cause.
Patients with this condition remain symptom less for a long period till the
restriction to blood flow is significant. The patient will seem tired and
unable to perform normal chores, and in extreme cases, it leads to
breathlessness and fainting.
The research group under
Deb is working towards simple solutions to heart calcification that occurs
after heart injury. Disruption of calcification using small molecules is a key
focus area along with research into identifying drugs that would disrupt ENPP1.
The focus of the research is more tuned towards reversal of calcification
rather than prevention of calcification.
- Aortic Valve Stenosis - (http://www.heart.org/HEARTORG/Conditions/More/HeartValveProblemsandDisease/Problem-Aortic-Valve-Stenosis_UCM_450437_Article.jsp#.WDJXabJ97IU)