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AssigneeThe Regents of the University of Colorado, a body corporate
InventorsMichael BRISTOW, Carmen SUCHAROV, Matthew TAYLOR, Dobromir SLAVOV
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Chronic activation of the β-Adrenergic Receptor (β-AR) can have deleterious effects on the heart, and animal models over-expressing the β-AR develop heart failure. In the classical β-AR pathway, activation of the receptor results in increased cyclic AMP(cAMP) levels. However, β-ARs are desensitized in the failing heart and cAMP levels are decreased. Phosphodiesterase 3A (PDE3A) hydrolyzes cAMP in certain subcellular compartments in cardiac myocytes, regulating cAMP levels and subsequent protein kinase A mediated cell signaling. By virtue of being freely diffusable intracellularly and being reduced in failing myocardial tissue, cAMP is reduced in certain important cardiac myocyte subcellular compartments such as the microdomain occupied by phospholamban.
A method of prophylactically treating heart failure comprising treating a subject after the subject is determined to exhibit a −1130 to −1159 deletion polymorphism in the promoter of a phosphodiesterase type 3A (PDE3A) gene, wherein said treating does not comprise a PDE3A inhibitor.
A method for predicting development of heart failure in a subject not suffering from heart failure comprising analyzing a biological sample from the subject for the presence of a −1130 to −1159 insertion/deletion polymorphism in the promoter of one or more phosphodiesterase type 3A (PDE3A) genes of the subject, wherein a subject determined to be homozygous or heterozygous for the deletion polymorphism is at increased risk of developing heart failure as compared to an individual who is homozygous for the insertion polymorphism.
A method for treating early stage heart failure in a subject comprising treating a subject after the subject is determined to exhibit a −1130 to −1159 deletion polymorphism in the promoter of phosphodiesterase type 3A (PDE3A) gene, wherein said treating does not comprise a PDE3A inhibitor.
Dependencies are inferred from the claim text.