LYVE1+ Macrophages Regulate Collagen Content in the Mitral Valve

Abstract

Regulation of cardiac extracellular matrix (ECM) is crucial to an organism’s overall health. Valvular ECM composition is important because valves maintain blood pressure and direction of flow. If the mitral valve becomes inflexible, it decreases blood flow in the body. Valvular stability and flexibility necessitate ECM proteins such as collagen, which must be regulated. Without regulation, a buildup of ECM proteins can occur. Many essential cardiovalvular regulatory mechanisms are poorly understood. However, regulation of collagen by specialized resident macrophages has been seen in arteries. Hyaluronan receptors (LYVE1) are present on specialized macrophages that, when bound, release matrix metalloproteinases (MMPs) that proteolyse collagen. To further our understanding on valvular flexibility, we used cross-sections of mitral valves from Lyve1-cre x Csf1r-floxed mouse models to compare mice with LYVE1+ macrophages to mice with depletion of LYVE1+ macrophages. We hypothesized that when LYVE1+ macrophages are depleted, there will be increased collagen content in the mitral valve. We found through picrosirius red staining and analysis that mice with LYVE1+ macrophages contain less collagen in the mitral valve when compared to mice where LYVE1+ macrophages were depleted. This indicates that LYVE1+ macrophages assist in the maintenance of ECM composition.