Matrix metalloproteinase 7 is associated with symptomatic lesions and adverse events in patients with carotid atherosclerosis.

Abstract

BACKGROUND:

Atherosclerosis is a major cause of cerebrovascular disease. Matrix metalloproteinases (MMPs) play an important role in matrix degradation within the atherosclerotic lesion leading to plaque destabilization and ischemic stroke. We hypothesized that MMP-7 could be involved in this process.

METHODS:

Plasma levels of MMP-7 were measured in 182 consecutive patients with moderate (50-69%) or severe (≥70%) internal carotid artery stenosis, and in 23 healthy controls. The mRNA levels of MMP-7 were measured in atherosclerotic carotid plaques with different symptomatology, and based on its localization to macrophages, the in vitro regulation of MMP-7 in primary monocytes was examined.

RESULTS:

Our major findings were (i) Patients with carotid atherosclerosis had markedly increased plasma levels of MMP-7 compared to healthy controls, with particularly high levels in patients with recent symptoms (i.e., within the last 2 months). (ii) A similar pattern was found within carotid plaques with markedly higher mRNA levels of MMP-7 than in non-atherosclerotic vessels. Particularly high protein levels of MMP-7 levels were found in those with the most recent symptoms. (iii) Immunhistochemistry showed that MMP-7 was localized to macrophages, and in vitro studies in primary monocytes showed that the inflammatory cytokine tumor necrosis factor-α in combination with hypoxia and oxidized LDL markedly increased MMP-7 expression. (iv) During the follow-up of patients with carotid atherosclerosis, high plasma levels of MMP-7 were independently associated with total mortality.

CONCLUSION:

Our findings suggest that MMP-7 could contribute to plaque instability in carotid atherosclerosis, potentially involving macrophage-related mechanisms.

• Authors: Azhar Abbas, Pål Aukrust, David Russell, Kirsten Krohg-Sørensen, Trine Almås, Dorte Bundgaard, Vigdis Bjerkeli, Ellen Lund Sagen, Annika E Michelsen, Tuva B Dahl, Sverre Holm, Thor Ueland, Mona Skjelland, Bente Halvorsen
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e84935 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24400123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Matrix Metalloproteinase 7

Topics

• Aged
• Carotid Artery Diseases (genetics, metabolism, mortality, pathology)
• Carotid Stenosis (genetics, metabolism, pathology)
• Case-Control Studies
• Female
• Gene Expression
• Humans
• Male
• Matrix Metalloproteinase 7 (blood, genetics, metabolism)
• Middle Aged
• Monocytes (metabolism)
• Plaque, Atherosclerotic (metabolism)
• Prognosis
• Risk Factors