Abstract
Atherosclerosis is an inflammatory disease involving, among others, production and degradation of the extracellular matrix and the accumulation of lipids in the arterial wall. Matrix metalloproteinases (MMPs) are the main physiological mediators of matrix degradation, capable of degrading extracellular matrix components such as collagens, proteoglycans, elastin, laminin, fibronectin, and other glycoproteins. The actions of MMPs could potentially be modulated with different approaches: (1) inhibition of MMP expression and protein synthesis, (2) inhibition of MMP activation, and (3) inhibition of MMP activity.1 Although subject for studies for many years, including the development of more specific inhibitors for different MMP family members such as MMP-8 and MMP-12, opportunities as useful therapeutic targets in clinical studies are still hampered. The effect of broad-spectrum MMP inhibitors has been studied in models of vascular injury in large animal studies with varying outcomes. MMP inhibition results in impaired constrictive remodeling after balloon angioplasty2 but fails to inhibit in stent neointima formation.3 Interfering with MMP activity has been a popular approach to attenuate atherosclerotic disease in animal models, but translation to human disease is cumbersome. There are many reasons to explain this failure in translation: expression patterns of MMPs and TIMPs (tissue inhibitor of metalloproteinases) in mouse and human macrophages differ, and the lack of adequate preclinical models is evident. In addition, the widespread functional relevance of MMPs in human biology hamper clinical application because of side effects.4 However, currently clinically applied drugs …
Highlights
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association
MicroRNAs are small regulatory noncoding RNA molecules, 19 to 22 nucleotides in length, which bind to the 3′-untranslated region of the mRNAs and regulate mRNA expression via degradation or inhibition of their translation. miRNAs are thereby able to post-transcriptionally regulate protein levels
Evidence is accumulating showing important functional roles for miRNAs in cardiovascular disease, including atherosclerosis[5] and aneurysm formation,[6] which were recently extensively reviewed. miRNAs have been associated with cardiovascular disease risk factors, including hyperlipidemia, hypertension, obesity, diabetes mellitus, lack of physical activity, and smoking
Summary
Correspondence to Gerard Pasterkamp, MD, PhD, Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands. Evidence is accumulating showing important functional roles for miRNAs in cardiovascular disease, including atherosclerosis[5] and aneurysm formation,[6] which were recently extensively reviewed.
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