E-selectin-targeted copolymer reduces atherosclerotic lesions, adverse cardiac remodeling, and dysfunction

Journal of Controlled Release : Official Journal of the Controlled Release Society
Olga TsorefJonathan Leor

Abstract

Endothelial activation with up-regulation of E-selectin adhesion molecules mediates leukocyte rolling along the vascular wall and controls inflammation in many diseases including atherosclerosis and heart failure. Therefore, we aimed to test the hypothesis that inhibition of E-selectin-mediated interactions by a new E-selectin-targeted copolymer could inhibit the progression of atherosclerosis. To target E-selectin on activated endothelium, we developed a new N-(2-hydroxypropyl)methacrylamide (HPMA)-based E-selectin binding copolymer with or without dexamethasone (Dex) (designated P-(Esbp)-Dex and P-Esbp, respectively). To determine the effect of P-(Esbp)-Dex and P-Esbp on atherosclerosis, we allocated ApoE (-/-) mice on a high fat diet, to weekly intra-peritoneal injections of either 1) P-Esbp; 2) P-(Esbp)-Dex; 3) free Dex (1 mg/kg) or 4) saline, for four weeks. Aortic atherosclerosis and left ventricular (LV) remodeling and function were assessed by serial ultrasound studies and histology. Monocytes and macrophages were characterized by flow cytometry. After four weeks of treatment, P-Esbp effectively targeted aortic atherosclerotic lesions. Both P-Esbp and P-(Esbp)-Dex reduced wall thickening of the ascending aortas. However...Continue Reading

Citations

Aug 10, 2019·Current Pathobiology Reports·Ana CartayaEdward M Bahnson
Aug 1, 2020·Advanced Drug Delivery Reviews·Jindřich Kopeček, Jiyuan Yang
Nov 19, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Marie RütterAyelet David
Mar 11, 2021·International Journal of General Medicine·Jin LiShujuan Tian
May 14, 2021·Advanced Drug Delivery Reviews·Fabiana PassaroGianluca Testa
May 20, 2021·Macromolecular Bioscience·Marina Rodrigues TavaresTomáš Etrych
Jun 23, 2021·ESC Heart Failure·Anne RaafsStephane Heymans

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