Array lessons from the heart: focus on the genome and transcriptome of cardiomyopathies

Despina Sanoudou, Elizabeth Vafiadaki, Demetrios A. Arvanitis, Evangelia Kranias, Aikaterini Kontrogianni-Konstantopoulos
2005 Physiological Genomics  
Our understanding of the cardiovascular system has evolved through the years by extensive studies emphasizing the identification of the molecular and physiological mechanisms involved in its normal function and disease pathogenesis. Major discoveries have been made along the way. However, the majority of this work has focused on specific genes or pathways rather than integrative approaches. In cardiomyopathies alone, over 30 different loci have shown mutations with varying inheritance patterns,
more » ... yet mostly coding for structural proteins. The emergence of microarrays in the early 1990s paved the way to a new era of cardiovascular research. Microarrays dramatically accelerated the rhythm of discoveries by giving us the ability to simultaneously study thousands of genes in a single experiment. In the field of cardiovascular research, microarrays are having a significant contribution, with the majority of work focusing on end-stage cardiomyopathies that lead to heart failure. Novel molecular mechanisms have been identified, known pathways are seen under new light, disease subgroups begin to emerge, and the effects of various drugs are molecularly dissected. This cross-study data comparison concludes that consistent energy metabolism gene expression changes occur across dilated, hypertrophic, and ischemic cardiomyopathies, while Ca 2ϩ homeostasis changes are prominent in the first two cardiomyopathies, and structural gene expression changes accompany mostly the dilated form. Gene expression changes are further correlated to disease genetics. The future of microarrays in the cardiomyopathy field is discussed with an emphasis on optimum experimental design and on applications in diagnosis, prognosis, and drug discovery. microarrays; heart failure; calcium homeostasis; structural components; metabolism 35%), conditions such as hypertension (ϳ17%) , aortic valve pathology (ϳ13%), and hereditary gene defects (ϳ20%) are the main underlying causes that can provoke extensive cardiac remodeling and perturb cardiac function (4, 39, 86, 105). Additionally, viral infection, neoplastic diseases, cytotoxic drugs, inflammation, hyperthyroidism, chronic alcohol abuse, metabolic diseases, systemic disorders, collagen vascular disease, physical agents, and late pregnancy may accelerate the Article published online before print. See web site for date of publication
doi:10.1152/physiolgenomics.00259.2004 pmid:15831843 fatcat:mas6ktj5vnb7vdcxqu3nm5vrri