Hope for Prevention of Heart Calcification After Heart Injury

Highlights

• Heart 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% of calcification.
• 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 heart.

Calcification

Calcification of the bone gives bones its strength and there is rarely calcification outside of the bones. However, there is calcification of blood vessels, 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.

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 process."

Genetically 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 forming cells.

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 dish.

ENPP1 (Ectonucleotide Pyrophosphatase / Phosphodiesterase 1)

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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 injected.

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."

Soft Tissue Calcification of the Heart

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Soft tissue 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.

Reference:

1. Aortic Valve Stenosis - (http://www.heart.org/HEARTORG/Conditions/More/HeartValveProblemsandDisease/Problem-Aortic-Valve-Stenosis_UCM_450437_Article.jsp#.WDJXabJ97IU)

Source-Medindia