Journal article
Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis
Nature communications, Vol.15(1), 8034
09/13/2024
DOI: 10.1038/s41467-024-52005-1
PMCID: PMC11399336
PMID: 39271657
Abstract
Atherosclerosis is an inflammatory disorder responsible for cardiovascular disease. Reactivation of efferocytosis, the phagocytic removal of cells by macrophages, has emerged as a translational target for atherosclerosis. Systemic blockade of the key ‘don’t-eat-me’ molecule, CD47, triggers the engulfment of apoptotic vascular tissue and potently reduces plaque burden. However, it also induces red blood cell clearance, leading to anemia. To overcome this, we previously developed a macrophage-specific nanotherapy loaded with a chemical inhibitor that promotes efferocytosis. Because it was found to be safe and effective in murine studies, we aimed to advance our nanoparticle into a porcine model of atherosclerosis. Here, we demonstrate that production can be scaled without impairing nanoparticle function. At an early stage of disease, we find our nanotherapy reduces apoptotic cell accumulation and inflammation in the atherosclerotic lesion. Notably, this therapy does not induce anemia, highlighting the translational potential of targeted macrophage checkpoint inhibitors.Systemic blockade of CD47 showed promising results for treating atherosclerosis but induces anemia. Here, the authors show that macrophage-specific nanoparticles promoting efferocytosis reduce apoptotic cell accumulation and inflammation in a porcine model of atherosclerosis without causing anemia.
Details
- Title: Subtitle
- Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis
- Creators
- Sharika Bamezai - Stanford UniversityYapei Zhang - Michigan State UniversityManisha Kumari - Michigan State UniversityMozhgan Lotfi - Stanford UniversityTom Alsaigh - Stanford UniversityLingfeng Luo - Stanford UniversityGayatri Suresh Kumar - Stanford UniversityFudi Wang - Stanford UniversityJianqin Ye - Stanford UniversityMadhu Puri - Michigan State UniversityRomila Manchanda - Michigan State UniversitySesha Paluri - Michigan State UniversityShaunak S Adkar - Stanford UniversityYoko Kojima - Stanford UniversityAlice Ingelsson - Stanford UniversityCaitlin F Bell - Stanford UniversityNicolas G Lopez - Stanford UniversityChanghao Fu - Stanford UniversityRyan B Choi - Stanford UniversityZach Miller - Michigan State UniversityLeo Barrios - Michigan State UniversitySusan Walsh - University of IowaFerhaan Ahmad - University of IowaLars Maegdefessel - Klinikum rechts der IsarBryan Ronain Smith - Michigan State UniversityNicholas J Leeper - Stanford University
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.15(1), 8034
- DOI
- 10.1038/s41467-024-52005-1
- PMID
- 39271657
- PMCID
- PMC11399336
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group
- Grant note
- Marian Falk Medical Research Trust Transformational Award: R01CA244491 National Institutes of Health: EIA34770065, 18TPA34230113
This work was supported by the Falk Foundation (Dr. Ralph and Marian Falk Medical Research Trust Transformational Award to N.J.L.), National Institutes of Health (R35 HL144475 to N.J.L.), the American Heart Association (EIA34770065 to N.J.L.; 18TPA34230113 to B.R.S.), the National Institutes of Health (R01CA244491 to B.R.S.), the Greathouse Family Foundation (to N.J.L.), Perkin-Elmer Post-doctoral Fellowship (to Y.Z.), and the Sarnoff Cardiovascular Research Foundation (to S.B.). We also acknowledge Exemplar Genetics, and especially the contributions of Katie DeKruyff, for their support with designing and conducting the pig experiments.
- Language
- English
- Date published
- 09/13/2024
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984704839102771
Metrics
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