In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 93, No. 5 ( 2003-09-05), p. 464-471
Abstract:
The myxoma virus protein Serp-1 is a member of the serine protease inhibitor superfamily. Serp-1 potently inhibits human serum proteases including plasmin, urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA). Serp-1 also displays a high antiinflammatory activity, rendering it a promising candidate for antiatherosclerotic therapy. In this study, we have thus examined the effect of Serp-1 on de novo atherosclerotic plaque formation and on advanced lesions. Perivascular collars were placed around carotid arteries of ApoE −/− mice to induce atherosclerotic plaques and Serp-1 treatment started at week 1 and week 5 after collar placement. Effects of Serp-1 on de novo atherogenesis were characterized by a significantly lower plaque size than that of control mice (18±5×10 3 versus 57±12×10 3 μm 2 , respectively; P =0.007). Immunostaining showed a 50% ( P =0.004) decrease in the MOMA-2–stained lesion area of Serp-1–treated mice. Treatment of advanced lesions with Serp-1 resulted in a decrease in plaque size and lumen stenosis ( P =0.028). α-Actin staining of these lesions was significantly increased compared with the control ( P =0.017). In both studies, a higher cellularity of the plaque and increased collagen content was observed in Serp-1–treated mice. In vitro studies showed that Serp-1 induces proliferation and migration of vascular smooth muscle cells. In conclusion, Serp-1 inhibits carotid artery plaque growth and progression in ApoE −/− mice. Equally relevant, it enhances cellularity of the plaque core potentially leading to improved plaque stability. The above results indicate that Serp-1 constitutes a promising lead in antiatherosclerotic therapy.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000090993.01633.D4
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
1467838-X
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