Found: Key ’go between’ in heart disease

Medical researchers at UNSW have shed light on a little-known mechanism involved in the thickening of arteries, a process associated with heart disease.

“Essentially we’ve uncovered a complex network of how one bad guy regulates another bad guy,” said Professor Levon Khachigian, of the Centre for Vascular Research (CVR) at UNSW. “We’ve also found a key to stopping this Mafioso network.”

Arteries thicken when tiny molecules are increased in blood vessels. These are known as ’growth factors’, which make the space in the arteries narrower and make it harder for blood to pass through.

The team’s research focuses on one of four parts that make up a certain growth factor family known as PDGF. The work relates to the D chain of that growth factor.

“Our investigations have found that a key peptide hormone called angiotensin controls the expression of an important part of PDGF,” said Professor Khachigian.

“Angiotensin has long been implicated in cardiovascular ailments like high blood pressure, restenosis and atherosclerosis,” he said. “Angiotensin uses a couple of ’middle men’ in the cell to jack up levels of PDGF D chain.”

“These ’go betweens’ are crucial to angiotensin’s mode of action,” he said. “If we take out these middle men (actually called transcription factors) we can greatly limit production of the growth factor, which is the result we would hope to see clinically.”

“Our findings will provide future opportunities to tease out more specific inhibitors of growth factor production in order to reduce the incidence of common vascular disorders.”

This is the first time PDGF D control has been studied at this molecular level.

The paper Inducible Platelet-Derived Growth Factor D-chain Expression by Angiotensin II and Hydrogen Peroxide Involves Transcriptional Regulation by Ets-1 and Sp1, has just been published in the influential international journal Blood.

The research was funded by the National Health and Medical Research Council.