Document Detail


Cytochrome P450 and ischemic heart disease: current concepts and future directions.
MedLine Citation:
PMID:  24274646     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Introduction: The P450 enzymes (P450s) mediate the biotransformation of several drugs, steroid hormones, eicosanoids, cholesterol, vitamins, fatty acids and bile acids, many of which affect cardiovascular homeostasis. Experimental studies have demonstrated that several P450s modulate important steps in the pathogenesis of ischemic heart disease (IHD). Areas covered: This article discusses the current knowledge on i) the expression of P450s in cardiovascular and renal tissues; ii) the role of P450s in the pathophysiology of IHD, in particular the modulation of blood pressure and cardiac hypertrophy, coronary arterial tone, ischemia-reperfusion injury and the metabolism of cardiovascular drugs; iii) the available evidence from observational studies on the association between P450 gene polymorphisms and risk of myocardial infarction (MI); and iv) suggestions for further research in this area. Expert opinion: P450s exert important modulatory effects in experimental models of IHD and MI. However, observational studies have provided conflicting results on the association between P450 genetic polymorphisms and MI. Further, adequately powered studies are required to ascertain the biological and clinical impact of P450s on clinical IHD end-points, that is, fatal and nonfatal MI, revascularization and long-term outcomes post MI. Pharmacogenetic substudies of recently completed cardiovascular clinical trials might represent an alternative strategy in this context.
Authors:
Andrew Rowland; Arduino A Mangoni
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-25
Journal Detail:
Title:  Expert opinion on drug metabolism & toxicology     Volume:  -     ISSN:  1744-7607     ISO Abbreviation:  Expert Opin Drug Metab Toxicol     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101228422     Medline TA:  Expert Opin Drug Metab Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Flinders University, School of Medicine, Department of Clinical Pharmacology , Bedford Park, SA 5042 , Australia.
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