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

• DOI: 10.1161/circresaha.111.240515
• Publication Date: 2011-02-04T04:17:08Z
• Authors: Stephan Zeibig; Zhongmin Li; Silvia Wagner; Hans-Peter Holthoff; Martin Ungerer; Andreas Bültmann; Kerstin Uhland; Jasmin Vogelmann; Thomas Simmet; Meinrad Gawaz; Götz Münch
• Keywords: Vulnerability; CD68; Vulnerable plaque

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