PAH Related Heart Dysfunction, Fibrosis May be Thwarted by Controlling Collagen Turnover

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A new study from investigators in Wisconsin suggests that treatments reducing the production and breakdown of collagen may be used as therapies for pulmonary arterial hypertension (PAH).

The research report “Limiting collagen turnover via collagenase‐resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension,” was published in the online journal Physiological Reports.

Simply, PAH is high blood pressure of the lungs. The condition worsens over time and is potentially fatal. Problems occur because too much pressure in the lung arteries strain the right heart ventricle – which leads to heart failure.

Although PAH currently has no cure, several medications including vasodilators can control symptoms including – but the treatments do not halt the progression of the disease.

Collagen deposits may occur in PAH due to scarring, but how it affects the heart’s right ventricle is not clear.

Study researchers, led by Mark J. Golob of the Department of Biomedical EngineeringUniversity of Wisconsin‐Madison College of Engineering, sought to understand how the synthesis and breakdown of collagen influences the heart’s right ventrical performance in people with PAH.

The scientists created genetically-modified mice, in which collagen is not easily degraded, and compared them to normal mice. They then deprived both sets of animals of oxygen, to experimentally induce PAH. Overall, the mice that did not have high collagen turnover had better heart function, and less degeneration of the right ventricle.

Researcher reported: “The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in (right ventricle) remodeling in response to chronic pressure overload.”

The study concluded that treatments that specifically block collagen turnover could potentially be used as therapies for PAH –  but further research is needed to first identify collagen-blocking agents, and then to test the agents for safe and effective treatment in humans.

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