Targeting pericytes for halting pulmonary hypertension in infants with congenital heart disease

Complete

04/11/2021

South West

Target validation, Drug discovery / Therapeutics

Awarded amount: £145,233

Grant scheme: TRP

Institution: University of Bristol

Principle Investigator: Prof Paolo Madeddu

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A ventricular septal defect is a type of congenital heart disease which occurs when the wall between the lower chambers of the heart does not develop properly.

If not corrected, this defect can cause a condition cause pulmonary hypertension (PAH), which is high blood pressure in the blood vessels around the lungs. This high blood pressure can cause the cells that wrap around the blood vessels of the lungs and heart, known as pericytes to contract. This means that the right-hand side of the heart has to overwork to pump blood through these vessels, causing them to eventually fail.

This project aimed to explore why these pericytes contract, causing the right heart to fail, and test some new potential treatments to prevent it.

The team compared normal pericytes with those from congenital heart disease and found that the CHD pericytes displayed a number of abnormal behaviours, including disproportional contraction and dying when exposed to angiotensin, a naturally occurring hormone that regulates blood pressure.

They also found that a protein that typically causes blood vessels to relax could potentially correct the pericytes sensitivity to angiotensin. This study has increased understanding of why PAH develops in congenital heart disease, and some potential routes of how this may be able to be treated.

Though this is early data, the results are promising, and this work is continuing alongside a number of collaborators. A publication is currently in progress and the results will be presented at a major conference next year.