Systems biology approaches to the study of cardiovascular drugs.
Atherogenic lipids and chronic inflammation drive the development of cardiovascular disorders such as atherosclerosis. Many cardiovascular drugs target the liver which is involved in the formation of lipid and inflammatory risk factors. With robust systems biology tools and comprehensive bioinformatical packages becoming available and affordable, the effect of novel treatment strategies can be analyzed more comprehensively and with higher sensitivity. For example, beneficial as well as adverse effects of drugs can already be detected on the gene and metabolite level, and prior to their macroscopic manifestation. This chapter describes a systems approach for a prototype CV drug with established beneficial and adverse effects. All relevant steps, for example, experimental design, tissue collection and high quality RNA preparation, bioinformatical analysis of functional processes, and pathways (targeted and untargeted) are addressed.
Nikolsky
Yuri
Y
GeneGo, Inc., St.Joseph, MI, USA.
Kleemann
Robert
R
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002317:Cardiovascular Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D012984:Software; D013223:Statistics as Topic; D013449:Sulfonamides / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D049490:Systems Biology / Q000379:methods*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D002317:Cardiovascular Agents; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012313:RNA; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides