Methods of reducing or preventing intimal damage caused by mechanical stimulation of endothelial cells
Inventors
Simard, J. Marc • Jacobson, Sven
Assignees
US Department of Veterans Affairs • Remedy Pharmaceuticals Inc
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Publication Number
US-10900040-B2
Publication Date
2021-01-26
Expiration Date
2036-05-25
Abstract
Embodiments of the disclosure encompass methods and/or compositions for ameliorating or preventing intimal damage caused by mechanical stimulation of endothelial cells. The damage may be caused by use of a device within an artery, vein, or capillary of an individual, such as to remove a thrombus, an embolus or an atherosclerotic plaque in the vessel. Treatment and prevention embodiments concern therapeutically effective amounts of one or more antagonists of the SUR1-TRPM4 channel that is upregulated upon the mechanical stimulation.
Core Innovation
The invention provides methods and/or compositions for ameliorating or preventing intimal damage caused by mechanical stimulation of endothelial cells. This damage may occur during use of a device within an artery, vein, or capillary, such as during removal of a thrombus, embolus, or atherosclerotic plaque. The methods involve administering therapeutically effective amounts of one or more antagonists of the SUR1-TRPM4 channel, which is upregulated upon mechanical stimulation of endothelial cells.
The problem solved by the invention is the lack of methods to reduce or prevent intimal damage in vessels caused by mechanical stimulation of endothelial cells. Mechanical stimulation during endovascular procedures can lead to upregulation of the SUR1-TRPM4 channel in endothelial cells, causing dysfunction and damage such as edema, hemorrhage, and intimal dissection. This invention addresses the need to prevent these deleterious effects to improve outcomes in vascular treatments involving mechanical devices.
Claims Coverage
The claims include one independent claim defining a method of inhibiting or reducing intimal damage by local administration of glibenclamide during catheter use.
Local administration of glibenclamide to reduce intimal damage
A method of inhibiting or reducing intimal damage caused by advancing a catheter through the vasculature of a subject, comprising administering a therapeutically effective amount of glibenclamide or its pharmaceutically acceptable salt solely locally to increase its local concentration in the blood vessel undergoing catheter advancement.
The claims focus on the inventive feature of locally administering glibenclamide to specifically increase local concentrations in vessels undergoing mechanical stimulation by catheter advancement, thereby inhibiting or reducing intimal damage caused by the procedure.
Stated Advantages
Prevention or reduction of intimal damage caused by mechanical stimulation during endovascular procedures.
Avoidance or amelioration of endothelial dysfunction, edema, hemorrhage, and intimal dissection in blood vessels.
Improved outcomes by preventing additional damage to tissues such as brain, heart, bowel, lung, or limb caused by edema or hemorrhage following mechanical stimulation.
Documented Applications
Prevention and treatment of intimal damage during catheter angiography.
Prevention and treatment of damage during mechanical thrombectomy procedures for removal of thrombus or embolus.
Prevention and treatment of intimal damage during endovascular aneurysm repair.
Use in cardiovascular applications including vascular endothelial cell protection after stent implantation in coronary, carotid, or peripheral arteries.
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