Chronic pulmonary volume overload increases lung MMP‐9 activity and is associated with pulmonary remodeling in mice.

Chronic heart volume overload increases pulmonary vascular pressure and may contribute to pulmonary remodeling associated with increased extracellular matrix (ECM) formation. We previously reported matrix metalloproteinase‐9 (MMP‐9) activation and cardiac tissue remodeling in a volume overload model of congestive heart failure in mice. We tested the hypothesis that in chronic cardiopulmonary overload, pulmonary remodeling involves ECM accumulation in response to MMP‐9 activation. Cardiopulmonary overload was created by arterio‐venous fistula (AVF) in wild type (B6/129, WT) and MMP‐9 knockout (FVB.Cg‐Mmp9 tm1Tvu /J, MMP9KO) mice. Mice were grouped as follows: WT, MMP9KO, WT+AVF, and MMP9KO+AVF (n=12). ECM accumulation and MMPs activity were measured in snap‐frozen sections of lung tissue by using Masson Trichrome and EnzChek Gelatinase assay kits. Compared to controls, AVF caused an increase in lung tissue MMPs activity and ECM accumulation in WT+AVF animals. Lungs from WT+AVF mice also had a greater lung/body weight coefficient. In contrast, in the MMP9KO+AVF group, these variables were significantly attenuated. These data suggest that pulmonary over‐perfusion can activate MMPs with subsequent ECM accumulation and pulmonary remodeling which could contribute to edema. Supported by ALA of KY and NIH HL‐74185.