دورية أكاديمية

Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis.

التفاصيل البيبلوغرافية
العنوان: Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis.
المؤلفون: Bamezai, Sharika, Zhang, Yapei, Kumari, Manisha, Lotfi, Mozhgan, Alsaigh, Tom, Luo, Lingfeng, Kumar, Gayatri Suresh, Wang, Fudi, Ye, Jianqin, Puri, Madhu, Manchanda, Romila, Paluri, Sesha, Adkar, Shaunak S., Kojima, Yoko, Ingelsson, Alice, Bell, Caitlin F., Lopez, Nicolas G., Fu, Changhao, Choi, Ryan B., Miller, Zach
المصدر: Nature Communications; 9/14/2024, Vol. 15 Issue 1, p1-13, 13p
مصطلحات موضوعية: ERYTHROCYTES, CD47 antigen, CARDIOVASCULAR diseases, NANOPARTICLES, CHEMICAL inhibitors
مستخلص: 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. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:20411723
DOI:10.1038/s41467-024-52005-1