Professor Julie McMullen

Identifying new risk markers and treatment strategies for the diseased heart

Professor Julie McMullen, Baker Heart and Diabetes Institute

2022 Vanguard Grant

Years funded: 2023-2023

When the heart enlarges in response to disease (e.g. hypertension) it is associated with impaired heart function. In contrast, when the heart enlarges in response to exercise it is associated with enhanced or preserved function. We identified that a protective gene in the heart called PI3K is critical for exercise, but not disease-induced heart enlargement in mouse models. We also showed that exercise and activating PI3K in the heart improves heart function in mouse models with heart disease. In contrast, lower PI3K in the hearts of mice leads to the development of heart failure prematurely. In humans, data is limited and this represents a knowledge gap.

AIM: To define lipid markers of PI3K activity in plasma samples from patients with a healthy heart compared to 2 different well-defined heart disease states: 1) severe aortic valve stenosis, and 2) heart failure.

EXPECTED OUTCOME & SIGNIFICANCE: Distinct regulation of PI3K markers in the healthy and diseased human heart which can help define cardiac risk and identify future treatment strategies.