Professor Kerry-Anne Rye

A new way to keep heart attack survivors healthy

Professor Kerry-Anne Rye, University of New South Wales

2020 Vanguard Grant

Years funded: 2021-2023

Heart attacks occur when a major artery is blocked by a blood clot. Heart attack survivors often have another heart attack within 5 years, progress to heart failure, and are up to six-times more likely to die of heart disease than a healthy person of comparable age. Current treatment options for reducing these adverse outcomes include preventing blood clots with anti-coagulants, lowering plasma LDL or “bad” cholesterol (LDL-C) levels with a statin, and decreasing blood pressure. Weight loss, stopping smoking, increasing physical activity and dietary improvements are also important, but compliance is frequently problematic.

However, LDL-C levels are often not sufficiently reduced in heart attack survivors, drugs that inhibit blood clot formation can increase the risk of bleeding, and blood pressure lowering drugs are useful only in patients with high blood pressure. These shortcomings highlight a major, unmet need for new therapeutic approaches to treat heart attack survivors. A potential strategy for achieving this goal is to reduce heart damage by inhibiting tissue inflammation and oxidation.

ApoA-I, the main protein in high density lipoproteins (HDLs), or “good” cholesterol, inhibits tissue inflammation and oxidation. However, levels of the inflammatory enzyme myeloperoxidase (MPO), which oxidises apoA-I and impairs its anti-inflammatory functions also increase after a heart attack. MPO additionally drives cardiovascular disease by oxidising LDLs, and impairing blood vessel function.

We have developed a clinically-viable peptide, D6PV, that mimics the anti-inflammatory properties of apoA-I. We also have access to a new class of potent MPO inhibitors, 2-thioxanthines, that protect proteins and peptides from oxidation by MPO. This project asks whether D6PV reduces inflammation after a heart attack, and whether this benefit is amplified by using D6PV with an MPO inhibitor. If successful, this project will deliver a new treatment regimen for heart attack survivors.