doi: 10.1161/ATVBAHA.107.146894
© 2007 American Heart Association, Inc.
Editorials |
A No-No for NonO and JNK in Extracellular Matrix Homeostasis and Vascular Stability
From the Department of Pathology and Laboratory Medicine, Genome Research Institute, University of Cincinnati College of Medicine, Ohio.
Correspondence to David Y. Hui, PhD, Department of Pathology and Genome Research Institute (ML 0507), University of Cincinnati, 2120 E. Galbraith Road, Cincinnati, OH 45237-0507. E-mail huidy@email.uc.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The pivotal role of chronic inflammation in the pathogenesis of atherosclerosis and aortic aneurysm is now firmly established.1 Atherosclerotic lesions usually develop at branch points in arteries with abnormal shear stress. Risk factors such as hypercholesterolemia, hypertension, and cigarette smoke, among others, promote injury to the vascular endothelium, resulting in the infiltration of leukocytes to initiate an inflammatory response. Monocytes infiltrating the lesion area accumulate lipids and become foam cells. Meanwhile, T lymphocytes populating the intimal area of the lesion secrete inflammatory cytokines such as 
-interferon (INF) and tumor necrosis factors (TNF) that further stimulate macrophages and activate vascular endothelial and smooth muscle cells. Chronic inflammation of the vessel wall attributable to repetitive endothelial injury advances lesion development with the deposition of extracellular matrix in forming a fibrous cap.
See page 1760
The coordinated regulation of extracellular matrix synthesis and degradation is essential for the maintenance of vascular homeostasis and plaque stability. Matrix metalloproteinases (MMPs) that degrade extracellular matrix promote atherosclerotic lesion formation by increasing smooth muscle cell migration and angiogenesis. Lesions with thin fibrous cap covering a necrotic core of dead cells are prone to fissures and rupture resulting in myocardial infarction. Likewise, the increase in MMP activities in the abdominal aorta also leads to the development of abdominal aortic aneurysm (AAA) and rupture.2,3 Stimuli that have been linked to inflammation and atherosclerosis are also observed in AAA, suggesting that these 2 vascular disease processes may have similar etiology and progression.
In the past 2 years, several studies have
Related Article:
Suppresses Prolyl-4-Hydroxylase 1 Expression via the ASK1–JNK–NonO Pathway
Arterioscler Thromb Vasc Biol 2007 27: 1760-1767.