Early Stage

2. PET Imaging Cardiac Inflammation in CD36-deficient Individuals

Introduction: Our study will assess myocardial inflammation in individuals with dysfunctional lipid metabolism using a novel non-invasive positron emission tomography (PET) imaging approach. Fatty acid (FA) translocase CD36 regulates myocardial FA uptake, remodeling and inflammation. CD36 deletion in rodents associates with atrioventricular block and bradycardia; and risk of sudden death following prolonged fasting. In humans, reduced or absent myocardial FA uptake is reported in people with CD36 variants that reduces protein levels. However, CD36 role in myocardial inflammation and remodeling, its contribution to heart disease, and whether preventive treatment strategies should be used in this population remain controversial due to lack of clinical studies.

Methods: Our studies will focus on carriers of the CD36 variants exclusive to African Americans. Targeted imaging of CCR2 positive proinflammatory monocytes/macrophages using PET/CT will be used. Freshly isolated circulating monocytes will be analyzed by flow cytometry.

Results: We hypothesize that partial or total CD36-deficient individuals are at higher risk of myocardial inflammations as compared to BMI-matched non-carrier individuals.

Impact: The study presents basic, translational and public health impact.
Biological Factors and products: This will be the first molecular imaging study assessing myocardial inflammation in obese individuals with CD36-deficiency and will provide a more integrative understanding of how immune cell subsets, CCR2 positive, drive myocardial inflammation during dysfunctional lipid metabolism. 
Biomedical Technology: Targeted PET tracer is a non-invasive imaging tool with the great potential to assess real-time trafficking of immune cells in the heart and to help identify immune-modulatory therapies.
Disease prevention and reduction: Establish risk stratification for cardiac inflammation based on genetically determined CD36 deficiency.
Public Health Practices: The proposed molecular imaging studies will be the first one conducted in CD36-deficient African Americans, who are at a higher risk of developing cardiovascular abnormalities from metabolic diseases.

Organization – Washington University in St. Louis

ACifarelli V, Liu Y, Abumrad NA, Gropler RJ