Vascular extracellular matrix in atherosclerosis

Abstract

The extracellular matrix (ECM) is an essential component of the human body that is responsible for the proper function of various organs. Changes in the ECM have been implicated in the pathogenesis of several cardiovascular conditions including atherosclerosis, restenosis, and heart failure. Matrix components, such as collagens and noncollagenous proteins, influence the function and activity of vascular cells, particularly vascular smooth muscle cells and macrophages. Matrix proteins have been shown to be implicated in the development of atherosclerotic complications, such as plaque rupture, aneurysm formation, and calcification. ECM proteins control ECM remodeling through feedback signaling to matrix metalloproteinases (MMPs), which are the key players of ECM remodeling in both normal and pathological conditions. The production of MMPs is closely related to the development of an inflammatory response and is subjected to significant changes at different stages of atherosclerosis. Indeed, blood levels of circulating MMPs may be useful for the assessment of the inflammatory activity in atherosclerosis and the prediction of cardiovascular risk. The availability of a wide variety of low-molecular MMP inhibitors that can be conjugated with various labels provides a good perspective for specific targeting of MMPs and implementation of imaging techniques to visualize MMP activity in atherosclerotic plaques and, most interestingly, to monitor responses to antiatheroslerosis therapies. Finally, because of the crucial role of ECM in cardiovascular repair, the regenerative potential of ECM could be successfully used in constructing engineered scaffolds and vessels that mimic properties of the natural ECM and consist of the native ECM components or composite biomaterials. These scaffolds possess a great promise in vascular tissue engineering.