Extracellular Matrix in Cardiovascular Pathophysiology: Proteomic Insights and Advancements to Mass Spectrometry-Based Characterization

Once thought of as only a supporting structure, the extracellular matrix (ECM) is now known to be a complex microenvironment that is critical to the maintenance of tissue structure and function. The ECM is made up of fibrillar structures, proteoglycans, matrix remodeling enzymes, signaling vesicles, pH-regulating ions, secreted metabolites, and glycoproteins. In a multitude of cardiovascular tissues, dysregulation of the ECM microenvironment is foundational to disease progression and a defined pathological feature of end-stage tissue failure. In this chapter, we aim to define the primary constituents of the ECM, review what is known about ECM structure in cardiovascular tissues in health and disease, and review recent original research in the field of cardiovascular proteomics, primarily human clinical cohorts of cardiovascular disease. While traditional mass spectrometry-based proteomic studies can identify ECM proteins and be probed for ECM dysregulation in the context of disease, there is an ongoing analytical challenge in the detection of the full extracellular matrisome. Finally, we aim to review advancements over the last decade in benchtop, mass spectrometry acquisition, and database search strategies to optimize ECM proteomics and discuss potential applications to the field of cardiovascular biology.