Prevention and treatment of cardiovascular pathologies

Abstract

A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): wherein Z is C═O or a covalent bond; Y is H or O(C 1 -C 4 )alkyl, R 1 and R 2 are individually (C 1 -C 4 )alkyl or together with N are a saturated heterocyclic group, R 3 is ethyl or chloroethyl, R 4 is H or together with R 3 is —CH 2 —CH 2 — or —S—, R 5 is I, O(C 1 -C 4 )alkyl or H and R 6 is 1, O(C 1 -C 4 )alkyl or H with the proviso that when R 4 , R 5 , and R 6 are H, R 3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to activate or stimulate production of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene and salts thereof. Further provided is a method for identifying a compound that is a TGF-beta activator or production stimulator is provided. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (I).

1 . A method for determining TGF-beta in vitro, thereby identifying a patient at risk for atherosclerosis or monitoring a recipient that has received one or more administrations of a TGF-beta activator or production stimulator, which method comprises: 
 (a) contacting a sample of blood serum or plasma from a patient or recipient with a capture moiety, to form a capture complex of said capture moiety and TGF-beta;    (b) contacting the capture complex with a detection moiety capable of binding TGF-beta and comprising a detectable label, or a binding site for a detectable label, to form a detectable complex; and    (c) detecting the presence of the detectable complex, thereby determining the presence of TGF-beta in said sample.    
   
   
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