Methods and compositions for treating atherosclerosis
AssigneeYale University
InventorsMichael SIMONS, Pei-Yu CHEN
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Abstract
In some aspects, the invention provides a method of treating atherosclerosis in a subject. The method comprises administering to the subject an agent that increases the activity or level of a let-7 miRNA or an agent that decreases activity or level of a TGFβ signaling polypeptide in an endothelial cell in the subject. In some embodiments, the subject is administered an additional agent comprising a therapeutically effective amount of rapamycin or any derivative thereof. In some embodiments, the agent is a let-7 miRNA. In some other aspects, the invention provides a pharmaceutical composition comprising a let-7 miRNA. In some embodiments, the let-7 miRNA is encapsulated in a nanoparticle formulated for selective delivery to an endothelial cell.
Claims53
A pharmaceutical composition comprising an effective amount of a let-7 miRNA in a nanoparticle formulated for selective delivery to an endothelial cell, in a pharmaceutically acceptable excipient.
A method of reducing an atherosclerotic lesion in a subject, the method comprising administering to the subject an agent that modulates the activity or level of let-7 miRNA in an endothelial cell in the subject, thereby reducing or inhibiting the atherosclerotic lesion in the subject.
A method of reducing an atherosclerotic lesion in a subject, the method comprising administering to the subject an agent that decreases in an endothelial cell in the subject the activity or level of a endothelial TGFβ signaling polypeptide selected from the group consisting of TGFβ1, TGFβ2, TGFβ3, TGFβR1, and TGFβR2, thereby reducing or inhibiting the atherosclerotic lesion in the subject.
A method of inhibiting progression of atherosclerosis in a subject, the method comprising administering to the subject an agent that increases the activity or level of let-7 miRNA in an endothelial cell in the subject, thereby inhibiting progression of atherosclerosis in the subject.
A method of inhibiting progression of atherosclerosis in a subject, the method comprising administering to the subject an agent that decreases in an endothelial cell in the subject the activity or level of a TGFβ signaling polypeptide selected from the group consisting of TGFβ1, TGFβ2, TGFβ3, TGFβR1, and TGFβR2, thereby inhibiting progression of atherosclerosis in the subject.
A method of reversing atherosclerosis in a subject, the method comprising administering to the subject an agent that increases the activity or level of let-7 miRNA in an endothelial cell in the subject, thereby reversing atherosclerosis in the subject.
A method of reversing atherosclerosis in a subject, the method comprising administering to the subject an agent that decreases in an endothelial cell in the subject the activity or level of a TGFβ signaling polypeptide selected from the polypeptide selected from the group consisting of TGFβ1, TGFβ2, TGFβ3, TGFβR1, and TGFβR2, thereby reversing atherosclerosis in the subject.
A method of treating atherosclerosis in a subject, the method comprising administering to the subject an agent that increases the activity or level of let-7 miRNA in an endothelial cell in the subject, thereby treating atherosclerosis in the subject.
A method of treating atherosclerosis in a subject, the method comprising administering to the subject an agent that decreases in an endothelial cell in the subject the activity or level of a TGFβ signaling polypeptide selected from the group consisting of TGFβR1, and TGFβR2, thereby treating atherosclerosis in the subject.
A method of inhibiting progression of atherosclerosis in a subject, the method comprising administering to the subject an agent that decreases the activity or level of FRS2α in a smooth muscle cell in the subject, thereby inhibiting progression of atherosclerosis in the subject.
A method of reversing atherosclerosis in a subject, the method comprising administering to the subject an agent that decreases the activity or level of FRS2α in a smooth muscle cell in the subject, thereby reversing atherosclerosis in the subject.
A method of treating atherosclerosis in a subject, the method comprising administering to the subject an agent that decreases the activity or level of FRS2α in a smooth muscle cell in the subject, thereby treating atherosclerosis in the subject.
A method of identifying an agent that modulates atherosclerosis, the method comprising measuring the activity or level of a TGFβ signaling polypeptide or polynucleotide, a let-7 miRNA, or a FGF signaling polypeptide or polynucleotide in a cell contacted with a candidate agent, wherein an alteration in the activity or level of the TGFβ signaling polypeptide or polynucleotide, the let-7 miRNA, or the FGF signaling polypeptide or polynucleotide relative to a reference indicates the candidate agent modulates atherosclerosis.
A method of reducing, inhibiting or reversing an endothelial-to-mesenchymal transition (EndMT) in an endothelial cell in a subject in need thereof, the method comprising administering to the subject an agent that decreases in the endothelial cell of the subject the activity or level of at least one selected from the group consisting of let-7 miRNA, endothelial TGFβ signaling polypeptide and FRS2α, thereby reducing, inhibiting or reversing the EndMT in the endothelial cell in the subject in need thereof.
A method of reducing, inhibiting or reversing an endothelial-to-mesenchymal transition (EndMT) in an endothelial cell in a subject in need thereof, the method comprising administering to the subject at least one siRNA that decreases in the endothelial cell of the subject the activity or level of at least one TGFβ receptor, thereby reducing, inhibiting or reversing the EndMT in the endothelial cell in the subject in need thereof.
Dependencies are inferred from the claim text.