Reduction in myocardial infarction size
This invention provides methods and compositions used for reducing the Myocaidial Infarct (MI) size in diabetic subjects exhibiting the haptoglobin (Hp) 2 allele. Specifically, the invention relates to reduction of MI in diabetic subjects carrying the Hp-2 allele by reducing the oxidative sterss in these subjects following ischemia-reperfusion injury.
1 . A method for treatment of a cardiovascular complication in a subject having the Hp-2 allele, comprising administering to said subject an effective amount of a compound, thereby reducing oxidative stress in said subject.
2 . The method of claim 1 , wherein said vascular complication is a myocardial infarct resulting from ischemia-reperfusion injury and wherein the treatment is reducing the size of said myocardial infarct (MI).
3 . The method of claim 1 , wherein said subject is diabetic.
4 . The method of claim 1 , wherein said treatment comprises treating, reducing incidence, or alleviating symptoms, eliminating recurrence, preventing recurrence, preventing incidence, improving symptoms, improving prognosis or combination thereof.
5 . The method of claim 3 , wherein said vascular complication is microvasculal complication or macrovascular complication.
6 . The method of claim 5 , wherein said macrovascular complication is a chronic heart failure, a cardiovascular death, a stroke, a myocardial infarction, a coronary angioplasty associated restenosis, a myocardial ischemia or a combination thereof.
7 . The method of claim 5 , wherein said microvascular complication is diabetic neuropathy, diabetic nephropathy or diabetic retinopathy.
8 . The method of claim 1 , wherein said compound is glutathione peroxidase, an isomer, a functional derivative, a synthetic analog, a pharmaceutically acceptable salt or a combination thereof.
9 . The method of claim 1 , preceded by determining the Hp phenotype in said subject.
10 . The method of claim 1 , comprising reducing the level of labile plasma iron (LPI) below 0.3 μM.
11 . The method of claim 1 , further comprising increasing the release of IL-10. in said subject.
12 . The method of claim 11 , wherein increasing the release of IL-10 is done by administrating to said subject an effective amount of Hp-1-1-Hb complex.
13 . The method of claim 12 , wherein said effective amount of Hp-1-1-Hb complex is between about 100 . to about 300 nM.
14 . The method of claim 13 , wherein said effective amount of Hp-1-1-Hb complex is about 150 nM.
15 . The method of claim 3 , comprising administering to said subject an effective amount of IL-10.
16 . A method of assessing the risk of developing large size myocardial infarction following ischemia reperfusion injury in a diabetic subject, comprising analyzing the Hp phenotype in said subject, wherein Hp 2 allele indicates a high risk of developing increased size myocardial infarct (MI).
17 . A composition for reducing the myocardial infarct in a diabetic subject carrying the Hp 2 allele, comprising: glutathione peroxidase or an analog thereof and a pharmaceutically acceptable carrier, excipient, flow agent, processing aid, a diluent or a combination thereof.
18 . The composition of claim 17 , further comprising Hp-1-1-Hb complex in a concentration effective to increase release of IL-10 in said subject.
19 . The composition of claim 17 , further comprising IL-10.
20 . The composition of claim 17 , further comprising a chelating agent capable of reducing labile plasma iron in said subject.
21 . The composition of claim 20 , wherein said chelating agent is deferriprone (L1), EDTA, ICL670, ascorbate or a combination thereof.
22 . The composition of claim 17 , wherein said carrier; excipient, lubricant, flow aid, processing aid or diluent is a gum, a starch, a sugar, a cellulosic material, an aclylate, calcium carbonate, magnesium oxide, talc, lactose monohydrate, magnesium stearate, colloidal silicone dioxide or mixtures thereof.
23 . The composition of claim 17 , comprising a binder, a disintegrant, a buffet, a protease inhibitor, a surfactant, a solubilizing agent, a plasticizer, an emulsifier, a stabilizing agent, a viscosity increasing agent, a sweetner, a film forming agent, or any combination thereof.
24 . The composition of claim 17 , wherein said composition is in the form of a pellet, a tablet, a capsule, a solution, a suspension, a dispersion, an emulsion, an elixir, a gel, an ointment, a cream, or a suppository.
25 . The composition of claim 17 , wherein said composition is in a form suitable for oral, intravenous, intraaorterial, intramuscular, subcutaneous, parentetal, transmucosal, transdermal, or topical administration.
26 . The composition of claim 17 , wherein said composition is a controlled release composition.
27 . The composition of claim 17 , wherein said composition is an immediate release composition.
28 . The composition of claim 17 , wherein said composition is a liquid dosage form.
29 . The composition of claim 17 , wherein said composition is a solid dosage form.