Immunomodulation of atherosclerotic plaque macrophages by HDL nanobiologics

• Grant number: 18/14858-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: December 01, 2018
• End date: May 31, 2019
• Field of knowledge: Agronomical Sciences - Food Science and Technology - Food Science
• Principal Investigator: Inar Castro Erger
• Grantee: Bianca Scolaro
• Supervisor: Edward A. Fisher
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: NYU Langone Medical Center, United States
• Associated to the scholarship: 17/22198-8 - Dietary interventions and HDL anti-inflammatory activity: the potential to modulate macrophage polarization, BP.PD

Abstract

In recent years, immunotherapy has gained great attention. The principle of empowering a patient's immune system to perform its natural role - to fight disease - has yet to be applied to reversing atherosclerosis and its clinical manifestations. Plaque regression as a result of LDL cholesterol lowering is very limited and the residual risk of cardiovascular events after treatment with statins remains unacceptably high. Therefore, new therapeutic strategies are needed to address risk factors beyond LDL-C, such as inflammation, in order to reverse atherosclerosis and reduce existing plaque burden. Increasing attention has also focused on HDL functionality as a cardioprotective approach. Previous research conducted by Dr. Edward Fisher's research team has shown that HDL can lead to a shift in macrophage phenotype from an inflammatory state (M1) towards an anti-inflammatory state (M2), in vivo and in vitro, and that polarization to the M2 state is required for resolution of atherosclerotic inflammation and plaque regression. In this proposal, our aim is to apply nanoimmunomodulation using a natural targeting concept: we propose to "reprogram" macrophages with HDL nanobiologics, which preferentially and efficiently bind to macrophages and can also direct immunomodulatory molecules directly to these cells. Therefore, we will test the effect of HDL delivery of M2-phenotype agonists to plaque macrophages in atherosclerotic Apoe-/- mice.