Crossing Into the Next Frontier of Cardiac Extracellular Matrix Research.

The extracellular matrix (ECM) is a complex and dynamic entity that drives the formation and development of the cardiovascular system, determines critical aspects of cardiovascular performance, and plays key roles in the initiation and progression of abnormal cardiovascular function with aging and disease. Microscopic studies in the late 1700s identified fibrous structures surrounding cells, which led scientists to conclude that the ECM was primarily a foundational unit to provide support. Unfortunately, this historic view that the ECM is a static scaffold is still to this day held by many who are not in the field. Using molecular, cell based, and dynamic imaging systems, however, experts now recognize that the ECM is an ever-changing component that responds to normal and abnormal molecular and biophysical cues and, in turn, drives changes in overall cardiovascular structure and function. The ECM contains structural and nonstructural proteins, interacts dynamically with unique and differentiating cell types, serves as a reservoir and processing site for signaling molecules, and forms communication corridors for both protein and genetic information. Thus, the ECM is a diverse entity that presents a novel and exciting research frontier that could yield improvements in diagnostics, prognostics, therapeutics, and prevention of cardiovascular disease. A recent Pubmed search (accessed August 23, 2016) using the terms ECM and cardiovascular, cardiac, or vascular revealed that this field has been growing annually since the 1990s (Figure). Driving forces for the increased interest in ECM research include the recognition of biological and pathophysiological importance, improvements in biochemical, cellular, and molecular techniques by which to study this complex unit, and advances in the capacity at microscopic and macroscopic levels to provide greater insight into the dynamically changing ECM. Using combinatorial approaches, ECM research can be explored at greater depths than previously possible. This editorial forms a coalescence of discussions by an ad-hoc panel motivated by a call by the American Heart Association to define important cardiovascular ECM research topic areas.