system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Aneurysm, Animals, Apolipoproteins E, Arteries, Atherosclerosis, Collagen, Dietary Fats, Elastin, Gene Expression, Humans, Lipids, Macrophages, Matrix Metalloproteinase 12, Matrix Metalloproteinase 13, Matrix Metalloproteinase 3, Mice, Mice, Inbred C57BL, Mice, Transgenic, Tissue Inhibitor of Metalloproteinase-1.
user
Are apolipoprotein E knockout mice over-expressing human tissue inhibitor of metalloproteinase 1 protected against aneurysm formation but not against atherosclerotic plaque development? Context: We investigated the effect of plasma levels of human tissue inhibitor of metalloproteinase (hTIMP)-1 on arterial lesion development and aneurysm formation in apolipoprotein-E-deficient mice (ApoE(-/-)). Control and transgenic mice were fed either a chow diet or a high-fat diet for 90 and 180 days. hTIMP-1 has a tendency to decrease atherosclerotic lesions, but did not attain significance (approximately 6% reduction in hTIMP-1(+/+), p = 0.075, and approximately 4% in hTIMP-1(+/0), p = 0.088 vs. control). Immunohistological and histological analyses revealed a reduction in macrophage accumulation (23% of control in hTIMP(+/0), p = 0.065, and 49% of control in hTIMP(+/+), p < 0.05) but not in collagen degradation within the lesion in transgenic mice. Moreover, elastin degradation in sites of pseudo-microaneurysms was reduced in transgenic mice (37% of control in hTIMP-1(+/0), p < 0.05, and 50% of control in hTIMP-1(+/+), p < 0.05). DNA array analysis of matrix metalloproteinase (MMP) expression followed by real-time PCR quantification revealed a significant up-regulation of MMP-3, MMP-12 and MMP-13 in arterial lesions of ApoE(-/-) mice fed a high-fat diet in comparison with the same mice fed a chow diet.
assistant
These data show that hTIMP-1 reduces aneurysm formation in ApoE(-/-) mice but does not protect them against the development of arterial lesions. Final Decision: yes