ENHANCED MEDICAL TREATMENTS RESULTING FROM CHEMICAL IDENTIFICATION OF CALCIUM INFLUX FACTOR, IDENTITY WITH THE FACTOR ACTIVATING PHOSPHOLIPOLYSIS AND PRECIPITATING SUDDEN DEATH DURING MYOCARDIAL INFARCTION, AND DETERMINATION OF SIMILAR ACTIVATING MECHANISMS IN MULTIPLE CELL TYPES THROUGH DISINHIBITION OF CALCIUM-INDEPENDENT PHOSPHOLIPASE A2beta

Abstract

A method for treating a mammal comprises administering at least one of a gene, enzyme and pharmaceutical which modulates the concentration of iPLA 2 β through transcriptional and/or translational regulation or effectively modulate the inhibition of iPLA 2 β through calmodulin or derivatives thereof.

1 . A method for treating a mammal, said method comprising administering a gene, enzyme or pharmaceutical which modulates the concentration of iPLA 2 β through transcriptional and/or translational regulation or effectively modulates the inhibition of iPLA 2 β through calmodulin or derivatives thereof.  
     
     
         2 . A method in accordance with  claim 1  wherein the mammal is a living human.  
     
     
         3 . A method in accordance with  claim 1  further comprising decreasing the intracellular content of acyl-CoA and the production of toxic species derived therefrom.  
     
     
         4 . A method in accordance with  claim 1  further comprising treating hypertension in the metabolic syndrome by increasing the hydrolysis acyl-CoA thereby promoting the inhibition of iPLA 2 β and the entry of calcium into the smooth muscle myocyte.  
     
     
         5 . A method for in accordance with  claim 1  further comprising reducing lipid accumulation or inflammation in the vessel wall by hydrolysis of acyl-CoA and/or capacitative calcium influx.  
     
     
         6 . A method for in accordance with  claim 1  further comprising treating obesity by facilitating the removal of fatty acids from fat cells by increased acyl-CoA hydrolysis.  
     
     
         7 . A method in accordance with  claim 1  further comprising strengthening the interaction between iPLA 2 β and calmodulin, resulting in a decrease in iPLA 2 β phospholipase A 2  activity.  
     
     
         8 . A method in accordance with  claim 1  further comprising disrupting the interaction between iPLA 2 β and calmodulin, resulting in an increase in iPLA 2 β phospholipase A 2  activity.  
     
     
         9 . A method in accordance with  claim 1  further comprising performing measurements of blood fatty acid and/or lysophospholipid levels by shotgun lipidomics analysis and determining that the treatment was successful when and if fatty acid/lysophospholipid levels are normalized or ischemic damage is decreased.  
     
     
         10 . A method in accordance with  claim 1  further comprising performing measurements of blood insulin and determining that the treatment was successful when and if blood glucose tolerance is normalized.  
     
     
         11 . A method in accordance with  claim 1  further comprising performing measurements utilizing positron emission tomography (PET) with radiolabeled neurotransmitter, and determining that the treatment was successful when and if neurotransmitter release is normalized.  
     
     
         12 . A method of regulating cellular processes dependent upon Ca 2+  influx or entry related to the activation or inhibition of iPLA 2 β, the method comprising at least one of the steps of reversing the interaction of iPLA 2 β with calcium-activated calmodulin in a subject, and enhancing the interaction of iPLA 2 β with Calcium-activated calmodulin.  
     
     
         13 . A method in accordance with  claim 12  wherein the subject is a living human.  
     
     
         14 . A method in accordance with  claim 12  wherein conditions presented are capable of being reversed.  
     
     
         15 . A method of reducing activation of iPLA 2 β during ischemia comprises promoting re-formation of the iPLA 2 β:CaM complex in a subject, and decreasing phospholipid hydrolysis and associated ischemic damage.  
     
     
         16 . A method in accordance with  claim 15  wherein the subject is a living human.  
     
     
         17 . A method in accordance with  claim 15  wherein conditions presented are capable of being reversed.