Roles for dual endothelin-1/angiotensin ii receptor (dear) in hypertension and angiogenesis

Abstract

The present application is directed to the identification of mutations and/or polymorphisms in the Dual Endothelin-1/Angiotensin II Receptor (Dear) that indicate susceptibility to, or show current affliction with, hypertension. Additionally, the present invention discloses methods for the modulation of angiogenesis via the regulation of Dear.

1 . A method for determining an individual's susceptibility to hypertension comprising:
 (a) obtaining a biological sample from a patient; and   (b) detecting the presence or absence of at least one mutation or polymorphism in the Dual Endothelin-1/Angiotensin II Receptor (Dear) in said tissue sample as compared to a control sample,   (c) determining whether the mutation or polymorphism increases the expression of Dual Endothelin-1/Angiotensin II Receptor (Dear), enhances the affinity of ET-1 binding to Dual Endothelin-1/Angiotensin II Receptor (Dear), enhances the affinity of VEGF-signal peptide (VEGFsp) binding to Dual Endothelin-1/Angiotensin II Receptor (Dear), or increases Dear-activation when Dear is stimulated with a ligand, wherein the presence of at least one of the mutations or polymorphisms indicates that the individual is susceptible to hypertension.   
     
     
         2 . A method for diagnosing hypertension comprising:
 (a) obtaining a biological sample from a patient; and   (b) detecting the presence or absence of at least one mutation or polymorphism in the Dual Endothelin-1/Angiotensin II Receptor (Dear) in said tissue sample as compared to a control sample;   (c) determining whether the mutation or polymorphism increases the expression of Dual Endothelin-1/Angiotensin II Receptor (Dear), enhances the affinity of ET-1 binding to Dual Endothelin-1/Angiotensin II Receptor (Dear), enhances the affinity of VEGF-signal peptide (VEGFsp) binding to Dual Endothelin-1/Angiotensin II Receptor (Dear), or increases Dear-activation when Dear is stimulated with a ligand, wherein the presence of at least one of the mutations or polymorphisms indicates that the individual has hypertension.   
     
     
         3 . The method of  claim 1  further comprising performing a polymerase chain reaction (PCR) to amplify the DEAR coding sequence. 
     
     
         4 . The method of  claim 2 , wherein the DEAR coding sequence is a human DEAR coding sequence and has at least 75% homology or identity to SEQ ID NO. 1. 
     
     
         5 . The method of  claim 1  further comprising:
 (a) isolating nucleic acid from the biological sample; and 
 (b) contacting the nucleic acid with at least one nucleic acid probe under selective hybridization conditions, wherein said probe preferentially hybridizes with a nucleic acid sequence comprising a Dear mutation or polymorphism, wherein the binding of the probe to the isolated nucleic acid indicates that the individual is susceptible to or currently has hypertension. 
 
     
     
         6 . A method for enhancing angiogenesis at a clinically relevant site in an individual comprising administering to said patient an effective amount of a Dual Endothelin-1/Angiotensin II Receptor (Dear) activator. 
     
     
         7 . The method of  claim 7 , wherein said clinically relevant site is selected from the group consisting of a wound, ulcer, diabetic ulcer, and a heart with coronary artery disease.