Abstract
The extracellular matrix (ECM) is a highly complex macromolecular network present in all tissues and organs. The ECM is continuously remodelling under an orchestrated process facilitated by many matrix-degrading and matrix-synthesising enzymes in both health and disease. Disturbance of this balance can be the result of or can lead to various diseases. In cardiovascular diseases (CVDs), changes to the ECM are evident in conditions including: atherosclerosis, myocardial infarction (MI), venous thromboembolism (VTE) and abdominal aortic aneurysm (AAA). ECM proteins and ECM regulating enzymes are differently expressed in various CVDs. Most importantly, the altered deposition, macromolecule arrangement and activity of the ECM makes it an attractive marker of disease onset, pathogenesis and progression. Many medical imaging modalities allow disease assessment by exploiting native image contrast, by using non-targeted or by using protein or cell specific (targeted) imaging probes. However, the ability to directly visualise and quantify changes in specific ECM proteins enhances our understanding of the biological role of these proteins, enables monitoring of disease progression and response to treatment and may improve patient diagnosis and allocation of personalised therapies. This review focuses on the biochemistry of the major extracellular matrix proteins and advancements in the development of ECM-targeted probes for molecular imaging of CVD, particularly for applications of molecular magnetic resonance imaging (MRI) and position emission tomography (PET) imaging.
Highlights
The extracellular matrix (ECM) plays a key role in multicellular organism development [1].Previously, it was believed that the ECM was an inert component that solely served to provide mechanical stability, but today, it is viewed as a highly dynamic system that undergoes constant remodelling with post-translational modifications of its molecular components [2,3]
ECM proteins are located within these two basic compartments (Figure 2): (i) interstitial connective tissue, that surrounds cells providing a structural matrix for the tissues and (ii) specialised basement membrane that separates the epithelium and the stroma and is involved in the matrix-cell interactions [15]
These two compartments of the ECM are characterised by different components with the interstitial matrix comprised of molecules, including type I collagen, fibronectin, proteoglycans (PGs), glycosaminoglycans (GAGs), tenascin C and elastin, whereas the basement membrane is comprised of type IV collagen, laminins and nidogen
Summary
The extracellular matrix (ECM) plays a key role in multicellular organism development [1]. During the early stages of development and in response to injury, the remodelling rate of the ECM is increased and involves various molecules, including but not exclusively limited to, integrins and matrix metalloproteins (MMPs) [5] and changes of intra- or extracellular tension forces [5]. Given the critical role of the extracellular matrix in both physiological homeostasis and pathological compensatory processes, the ECM has become an attractive new target for molecular imaging with applications in numerous diseases. There are several review articles that provide extensive coverage of the use of these imaging modalities in the context of imaging cardiac ECM [11,12]. This review aims to address the latest developments in the field of non-invasive imaging of ECM changes that are associated with CVD.
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