Heparin and Gene Microarrays as a New Pharmacodynamic Tool

摘要

Traditionally the effect of a drug on a tissue is measured by methods that are either limit d in scope or in information. Individual protein and mRNA levels measured by Northern and Western blotting or by Immunohistochemistry, while demonstrating an effect and providing some mechanistic description provide informa ion only on those targeted molecules. Likewise, morphometric analyses of tissues examine the gross tissue response, but provide little insight into the underlying mechanis ns responsible for the present state of the tissue. Gene micro-arrays allow the screening of thousands of mRNA expression levels in a single sample. This technique therefore yields data that is both tissue wide in scope and mechanistic in nature. This becomes especially useful when the drug being examined has effects beyond that of the desired effect. In this chapter, Heparin and its ability to inhibit intimal hyperplasia following arterial injury will serve as an example of a disease and inter /ention where gene microarrays can be applied as a new pha macodynamic tool. Heparin's function as an anticoagulant s well described, but it is also known to possess numerous o her functions that are less well understood. It is both the pleiotropic effects of Heparin and the complexity of vascular disease that make this an ideal situation for the use of gene microarrays to monitor the efficacy of an drug delivery method.