Method of altering vascular permeability and uses thereof
Provided here are methods of modulating vascular permeability by changing the mechanical properties of extracellular matrices (ECM) and methods of treatment of diseases, conditions and symptoms related to vascular permeability such as pulmonary edema and acute respiratory distress syndrome (ARDS). The modulation can be increasing or decreasing vascular permeability. Vascular leakage can be normalized by increasing or decreasing ECM stiffness depending on the baseline mechanical properties of the tissue or organ. Vascular permeability is altered by changing the mechanical properties of ECM by administering a lysyl oxidase modulating (LOX) agent.
1. A method of decreasing vascular permeability in a tissue or organ of a subject in need of treatment for a pulmonary disease selected from acute respiratory distress syndrome (ARDS), pulmonary edema, endotoxin-induced lung injury, pulmonary embolism, pleural effusion, or sepsis, the method comprising:
administering an agent that decreases the stiffness of the extracellular matrix (ECM) to a subject in need thereof wherein the agent is a lysyl oxidase (LOX) inhibitor selected from the group consisting of:
a lysyl oxidase (LOX) siRNA, a peptide having the sequence EDTSCDYGYHRRFA (SEQ ID NO: 1), or a purified antibody that binds specifically to the sequence EDTSCDYGYHRRFA (SEQ ID NO: 1).
2. The method of claim 1 , further comprising measuring the ECM in the subject before treatment.
3. The method of claim 1 , wherein the agent is administered via aerosol delivery into the subject's lung.