title: NCAM(CD56) and RUNX1(AML1) are up-regulated in human ischemic cardiomyopathy and a rat model of chronic cardiac ischemia.
abstract: Chronic myocardial ischemia is the leading cause of impaired myocardial contractility and heart failure. To identify differentially expressed genes in human ischemic cardiomyopathy (ICM), we constructed a subtracted cDNA library using specimens of ICM compared to normal human heart. Among 100 randomly sequenced clones, seven sequences represented recently identified candidate genes for differential expression in cardiac hypertrophy. A further clone without a known hypertrophy-association coded for the adhesion molecule NCAM(CD56). RNase protection assay, immunohistochemistry, and Western blotting revealed strong overexpression of NCAM(CD56) in all hearts with ICM (n = 14) compared to normal hearts (n = 8), whereas in congestive cardiomyopathy (CCM) (n = 8), hypertrophic obstructive cardiomyopathy (n = 2), myocarditis (n = 4), and sarcoidosis (n = 2), at most slight overexpression of NCAM(CD56) was observed. NCAM(CD56) overexpression abnormally involved the whole cell membrane and the cytoplasma of cardiomyocytes only inside and adjacent to ischemia-induced cardiac scars. Normal or hypertrophic fibers at a distance from ischemic scars were devoid of NCAM overexpression. Identical alterations were observed in an experimental rat ICM model, but not in normal nor in spontaneously hypertensive rat hearts. In search of NCAM(CD56)-related transcription factors we found RUNX1(AML1) up-regulation in ICM and detected RUNX1(AML1) binding within the NCAM(CD56) promoter by electromobility shift assay. We concluded that strong overexpression of NCAM(CD56) and RUNX1(AML1) is a constant and characteristic feature of cardiomyocytes within or adjacent to scars in ICM.
authors.affiliation: Institute of Pathology, University of Würzburg, Josef-Schneiderstrasse 2, 97080 Würzburg, Germany. stefan.gattenloehner@mail.uni-wuerzburg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.forename: Christiane
authors.initials: C
authors.lastname: Waller
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Burkhard-Dieter
authors.initials: BD
authors.lastname: Bültmann
authors.forename: Hans-Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002648:Child; D002908:Chronic Disease; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493727:Runx1 protein, rat; D014157:Transcription Factors