Title:

The potential antiatherogenic effect of doxycycline –nonselective inhibitor of matrix metalloproteinases - on experimental model of atherosclerosis – apoE-knockout mice

Author:

Pawłowska, Małgorzata

Subject:

matrix metalloproteinases ; doxycycline ; atherosclerosis ; apoE-knockout mice

Abstract:

Doxycycline at subantimicrobial doses inhibits matrix metalloproteinases (MMPs) activity, and is the only MMP sinhibitor which is widely available in clinical practice. The aim of the study was to reveal whether nonspecific MMPs inhibition by tetracycline could ameliorate development of atherosclerosis in apolipoprotein E (apoE)-knockout mice. 30 female 8-week-old apoE–knockout mice (in each group n=15) on background C57BL/6J, were studied. Experimental groups received the same diet as control, mixed with doxycycline in a dose of 1.5 mg/ kg b.w./ day. Cholesterol profile was not changed by the drug. Doxycycline (1.5 mg/ kg b.w./ day) attenuated atherogenesis, measured both by “en face” method (10.25 ±1.7% vs. 15.7 ± 2.0%, p<0.05) and “cross-section” method (66 254 ± 7 468 μm2 vs. 90 687 ± 8 521 mm2, p<0.05). Insitu zymography showed marked decrease of the extent of non-specific gelatinase activity in doxycycline-treated mice (65 996 ± 11 480 mm2, p<0.001). Inflammatory indicators: sVCAM-1, MCP-1, IL-6,IL-12 as well as SAA had tendency to decrease after doxycycline, however, they did not reach statistical significance. Organ bath did not show any endothelial dysfunction in experimental mice. To our knowledge, this is the first report that shows the effect of doxycycline on atherogenesis in apoE–knockout mice.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia ; choroby układu krążenia

Degree grantor:

Wydział Lekarski

Promoter:

Jawień, Jacek

Date:

2011

Date issued:

2011

Type:

Praca doktorska

Call number:

ZB-115826

Language:

pol

Access rights:

nieograniczony

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