Hyaluronan in Cardiac Disease: Implications for the Extracellular Matrix Beyond Collagen

The structure of the heart changes in response to physiological cues. Such intrinsic plasticity of the heart involves changes to the extracellular matrix (ECM) and supports the adaptation to physiologic excursions such as athletic performance and pregnancy. Likewise, the ability of the ECM is critical for wound healing in the heart following myocardial infarction. Considering the involvement of the matrix in health and disease, it follows that a deep understanding of its composition and regulation would accelerate our pace of developing therapeutic interventions for the heart. Yet, we understand little of the composition of cardiac ECM and how its regulated. One such matrix component, hyaluronan (HA), has received scant attention in the heart despite its abundance rivaling that of collagen. This review addresses the biological origins of HA and its impact on the heart. HA production is linked to intermediary metabolism and is produced in response to injury. Much remains to be resolved regarding its production and degradation. And, although there are insights from other fields, the extent to which HA impacts the function of potential target cells is far from resolved. This review will also address techniques and tools available to assess cardiac HA and highlight areas of opportunity in the field along with some limitations in literature.