کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5433686 1508993 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting and modulating infarct macrophages with hemin formulated in designed lipid-based particles improves cardiac remodeling and function
ترجمه فارسی عنوان
هدفگیری و مدولاسیون ماکروفاژهای انفارکتوس با هیمن که در ذرات طراحی شده مبتنی بر لیپیدها طراحی شده، ردسازی و عملکرد قلب را بهبود می بخشد
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
چکیده انگلیسی

Uncontrolled activation of pro-inflammatory macrophages after myocardial infarction (MI) accelerates adverse left ventricular (LV) remodeling and dysfunction. Hemin, an iron-containing porphyrin, activates heme oxygenase-1 (HO-1), an enzyme with anti-inflammatory and cytoprotective properties. We sought to determine the effects of hemin formulated in a macrophage-targeted lipid-based carrier (denoted HA-LP) on LV remodeling and function after MI.Hemin encapsulation efficiency was ~ 100% at therapeutic dose levels. In vitro, hemin/HA-LP abolished TNF-α secretion from macrophages, whereas the same doses of free hemin and drug free HA-LP had no effect. Hemin/HA-LP polarized peritoneal and splenic macrophages toward M2 anti-inflammatory phenotype. We next induced MI in mice and allocated them to IV treatment with hemin/HA-LP (10 mg/kg), drug free HA-LP, free hemin (10 mg/kg) or saline, one day after MI. Active in vivo targeting to infarct macrophages was confirmed with HA-LP doped with PE-rhodamine. LV remodeling and function were assessed by echocardiography before, 7, and 30 days after treatment. Significantly, hemin/HA-LP effectively and specifically targets infarct macrophages, switches infarct macrophages toward M2 anti-inflammatory phenotype, improves angiogenesis, reduces scar expansion and improves infarct-related regional function.In conclusion, macrophage-targeted lipid-based drug carriers with hemin switch macrophages into an anti-inflammatory phenotype, and improve infarct healing and repair. Our approach presents a novel strategy to modulate inflammation and improve infarct repair.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 257, 10 July 2017, Pages 21-31
نویسندگان
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