Artigo Acesso aberto Revisado por pares

Effect of the oxLDL Binding Protein Fc-CD68 on Plaque Extension and Vulnerability in Atherosclerosis

2011; Lippincott Williams & Wilkins; Volume: 108; Issue: 6 Linguagem: Inglês

10.1161/circresaha.111.240515

ISSN

1524-4571

Autores

Stephan Zeibig, Zhongmin Li, Silvia Wagner, Hans‐Peter Holthoff, Martin Ungerer, Andreas Bültmann, Kerstin Uhland, Jasmin Vogelmann, Thomas Simmet, Meinrad Gawaz, Götz Münch,

Tópico(s)

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Resumo

Rationale: There is strong evidence that oxidative modification of low-density lipoprotein (oxLDL) plays a critical role in atherogenesis and that oxLDL may profoundly influence the mechanical stability of atherosclerotic plaques. Objective: To block oxLDL, we designed, expressed, and tested Fc-CD68, a soluble oxLDL binding protein consisting of human Fc and the extracellular domain of the human oxLDL-binding receptor CD68. Methods and Results: Fc-CD68 bound with high specific affinity to oxLDL and strongly bound and colocalized with oxLDL in plaques. To study the effects of repeated administrations of Fc-CD68 on the progression of atherosclerosis and plaque vulnerability, 12- and 16-week old cholesterol-fed ApoE −/− mice received either Fc-CD68 (n=6) or Fc control protein (n=6 to 8) thrice weekly for 4 weeks. Macroscopic and histological analysis of Sudan red lipid staining showed strong and significant reduction of plaque extension in the aorta and in the aortic root, respectively. Histological analysis of pentachrome- and Sirius-stained sections of the brachiocephalic arteries of 20 week-old ApoE −/− mice revealed that Fc-CD68 significantly reduced the occurrence of spontaneous ruptures of established plaques by ≈20%, compared with Fc and drastically increased the collagen content of plaques. Furthermore, in immunostained sections of the brachiocephalic artery and the aortic root, Fc-CD68 reduced the infiltration of plaques with T lymphocytes, and macrophages by ≈50% and 30%, respectively. Conclusions: The oxLDL binding protein Fc-CD68 attenuates atherosclerosis and strengthens the stability of atherosclerotic plaques.

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