Disclosed are compositions and methods for triggering disease selective macropinocytosis. The compositions can serve as a marker of disease activity and as a trigger of enhanced macropinocytosis in tissues undergoing disease remodeling such as wound healing, cancer, PAH, inflammation, diabetes, Crohn's disease, ulcerative colitis, ankylosing spondylitis, diseases of the endometrium, psoriasis, irritable bowel syndrome, arthritis, fibrotic disorders, interstitial cystitis, autoimmune diseases, asthma, acute lung injury, and adult respiratory distress syndrome. The compositions can also serve as a receptor for disease selective cell penetrating peptides in the cells and extracellular matrix of diseased tissues.

Sequence-defined anti-SHBG and anti-IBP4 antibodies or antigen-binding fragments thereof are described. The antibodies are comprise heavy chain variable and light chain variable domains, each having sequence-specified complementarity determining regions (CDRs). Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies and sequence-defined epitopes of the antibodies.

The present invention provides compositions and methods for treating pulmonary hypertension. In one aspect, a method is included for increasing myocyte enhancer factor 2 (MEF2) activity in an endothelial cell comprising exposing the cell to a class IIa histone deacetylase inhibitor. In another aspect, a method is included for treating pulmonary hypertension, such as restoring MEF2 activity, in a subject in need thereof comprising administering to the subject a composition comprising a class IIa histone deacetylase inhibitor. Pharmaceutical compositions for treating pulmonary hypertension in a subject in need thereof and a kit for diagnosing, detecting and/or monitoring pulmonary hypertension are also included.

Some embodiments relate to nanoparticle probes for the detection of disease states in a patient or for tissue engineering. In some embodiments, the nanoparticle probe comprises one or more slip bonds that bind to a cell surface structure. In some embodiments, the binding of the nanoparticle probe is selective. In some embodiments, the nanoparticle probe binds to cells having a certain maximum glycocalyx thickness.

This invention provides a method of treating hypertension in a hypertensive subject, the method administering to the subject, an amount of a diuretic and an amount of a CYP 112 beta hydroxylase inhibitor once or twice per day, wherein the amounts taken together are sufficient to treat hypertension in the hypertensive subject when taken in combination with other antihypertensive agents. In particular, the method is sufficient to elicit a safe and robust reduction in hypertension (>10 mmHg reduction in systolic blood pressure) in the hypertensive subject.

This invention provides a method of treating hypertension in a hypertensive subject having a body mass index of at least 30, the method comprising administering to the subject a CYP 112 beta hydroxylase inhibitor once or twice per day in an amount sufficient to treat hypertension in the hypertensive subject.

Disclosed are pathogenic mechanisms in pulmonary hypertension and molecular inhibitors of the same. Particularly, GSTP1 (glutathione S-transferase P1) have been demonstrated as having a role in regulating the endothelial ISCU function in pulmonary hypertension. Accordingly, methods for treating pulmonary hypertension in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition that inhibits glutathione S-transferase P (GSTP1) and/or increasing ISCU expression are disclosed. The GSTP1 inhibitor can comprise a piperlongumine analog, such as BRD-K34222889, or a derivative thereof.