# US 2013/0157944 A1 · Treatment of Myocardial Infarction and Vascular Injury with Netrin-1 > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0157944 A1 - Document ID: US20130157944A1 - Status: Published application - Kind: A1 - Application number: 13/698,541 - Filed: 2011-05-27 - Published: 2013-06-20 - Earliest claimed: 2010-05-28 - Assignees: The Regents of the University of California - Inventors: Hua Cai - Web page: https://patentgrep.com/patent/US20130157944A1 ## CPC - A61K 38/18: Growth factors; Growth regulators - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links - A61P 7/06: Antianaemics - A61P 9/00: Drugs for disorders of the cardiovascular system - C07K 14/475: Growth factors; Growth regulators - C12N 5/0657: {Cardiomyocytes; Heart cells} - C12N 5/0691: {Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels} - C12N 5/0692: {Stem cells; Progenitor cells; Precursor cells} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Disclosed herein are methods for treating, inhibiting, or reducing ischemia/reperfusion injury of a cardiac tissue; increasing phosphorylation of ERK1/2 and/or eNOS in a cardiac tissue; treating, inhibiting, or reducing loss of NO; treating, inhibiting, or reducing uncoupling of NOS; increasing recoupling of NOS; treating, inhibiting, or reducing loss of DCC protein and mRNA expression in a cardiac tissue; decreasing or reducing the infarct size of a heart resulting from ischemia/reperfusion injury; decreasing or reducing superoxide production by a cardiac tissue caused by ischemia/reperfusion injury; treating, inhibiting, or reducing neointimal formation and restenosis; treating, inhibiting, or reducing apoptosis of mobilized endothelial progenitor cells; or a combination thereof of a blood vessel (such as an artery, a coronary artery, a vein, or a capillary) or a portion of the blood vessel in a subject which comprise the administration of netrin-1. ## Claims ### Claim 1 A method of decreasing or reducing the infarct size of a heart resulting from ischemia/reperfusion injury which comprises contacting the heart with netrin-1; attenuating superoxide production in the heart by contacting the heart with netrin-1; attenuating NOX4 expression in the heart by contacting the heart with netrin-1; reducing NOS uncoupling in the heart by contacting the heart with netrin-1; increasing NOS recoupling in the heart by contacting the heart with netrin-1; or a combination thereof ### Claim at position 2 2-26. (canceled) ### Claim 27 A method of treating, inhibiting or reducing a disease or a condition in a cardiac tissue, a heart, a blood vessel, an endothelial progenitor cell, or a vascular smooth muscle cell, which comprises which comprises administering netrin-1 to the cardiac tissue, the heart, the blood vessel, the endothelial progenitor cell, or the vascular smooth muscle cell. ### Claim 28 (depends on 27) The method of claim 27, wherein the infarct size of a heart is decreased or reduced, the superoxide production in the heart is attenuated, NOX4 expression in the heart is attenuated, NOS uncoupling in the heart is reduced, NOS recoupling in the heart, nitric oxide production in the cardiac tissue is increased, DCC-dependent activation of ERK1/2 and eNOS is stimulated, the amount of loss of NO by the cardiac tissue is reduced, NO production is increased in the cardiac tissue, phosphorylation of ERK1/2 and/or eNOS is increased in the cardiac tissue, the loss of DCC protein and mRNA expression is reduced in the cardiac tissue, superoxide production by the cardiac tissue is reduced, cell apoptosis is reduced, or a combination thereof results from the administration of netrin-1. ### Claim 29 (depends on 27) The method of claim 27, which further comprises administering sepiapterin to the cardiac tissue, the heart, the blood vessel, the endothelial progenitor cell, or the vascular smooth muscle cell. ### Claim 30 (depends on 27) The method of claim 27, wherein the disease or condition is an ischemia/reperfusion injury which is treated, inhibited, or reduced upon the administration of netrin-1. ### Claim 31 (depends on 27) The method of claim 27, wherein the disease or condition is mitochondrial damage which is treated, inhibited, or reduced upon the administration of netrin-1. ### Claim 32 (depends on 27) The method of claim 27, wherein the disease or condition is neointimal formation and restenosis which is treated, inhibited, or reduced upon the administration of netrin-1. ### Claim 33 (depends on 27) The method of claim 27, wherein the disease or condition is a vascular injury or vascular dysfunction which is treated, inhibited, or reduced upon the administration of netrin-1. ### Claim 34 (depends on 27) The method of claim 27, wherein the netrin-1 is administered before, during, or after the disease or condition. ### Claim 35 (depends on 27) The method of claim 27, wherein the netrin-1 is administered to a subject, preferably a mammalian subject, more preferably a human subject, having the cardiac tissue, the heart, the blood vessel, the endothelial progenitor cell, or the vascular smooth muscle cell. ### Claim 36 (depends on 27) The method of claim 27, wherein the netrin-1 is human netrin-1. ### Claim 37 (depends on 27) The method of claim 27, wherein the cardiac tissue is a heart, cardiomyocytes, or cardiac endothelial cells. ### Claim 38 (depends on 27) The method of claim 27, wherein the administration to the cardiac tissue, the heart, the blood vessel, the endothelial progenitor cell, or the vascular smooth muscle cell is in vitro or in vivo. ### Claim 39 (depends on 27) The method of claim 27, wherein the administration to the cardiac tissue, the heart, the blood vessel, the endothelial progenitor cell, or the vascular smooth muscle cell is systemic or local. ### Claim 40 (depends on 27) The method of claim 27, wherein the amount of netrin-1 is a therapeutically effective amount of netrin-1. ### Claim 41 A method of treating endothelial progenitor cells to reduce apoptosis resulting from exposure to oxidative stress or improve the quality of the endothelial progenitor cells prior to use in a cell-based therapy which comprises contacting the endothelial progenitor cells with netrin-1.