Abstract:
OBJECTIVES:The goal of this study was to identify genes upregulated in the heart in human patients with hypertrophic cardiomyopathy (HCM). BACKGROUND:Hypertrophic cardiomyopathy is a genetic disease caused by mutations in contractile sarcomeric proteins. The molecular basis of diverse clinical and pathologic phenotypes in HCM remains unknown. METHODS:We performed polymerase chain reaction-select complementary DNA subtraction between normal hearts and hearts with HCM and screened subtracted libraries by Southern blotting. We sequenced the differentially expressed clones and performed Northern blotting to detect increased expression levels. RESULTS:We screened 288 independent clones, and 76 clones had less than twofold increase in the signal intensity and were considered upregulated. Sequence analysis identified 36 genes including those encoding the markers of pressure overload-induced ("secondary") cardiac hypertrophy, cytoskeletal proteins, protein synthesis, redox system, ion channels and those with unknown function. Northern blotting confirmed increased expression of skeletal muscle alpha-actin (ACTA1), myosin light chain 2a (MLC2a), GTP-binding protein Gs-alpha subunit (GNAS1), NADH ubiquinone oxidoreductase (NDUFB10), voltage-dependent anion channel 1 (VDAC1), four-and-a-half LIM domain protein 1 (FHL1) (also known as SLIM1), sarcosin (SARCOSIN) and heat shock 70kD protein 8 (HSPA8) by less than twofold. Expression levels of ACTA1, MLC2a and GNAS1 were increased in six additional and FHL1 in four additional hearts with HCM. CONCLUSIONS:A diverse array of genes is upregulated in the heart in human patients with HCM, which could account for the diversity of clinical and pathologic phenotypes. Markers of secondary hypertrophy are also upregulated, suggesting commonality of pathways involved in HCM and the acquired forms of cardiac hypertrophy. Elucidation of the role of differentially expressed genes in HCM could provide for new therapeutic targets.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Lim DS,Roberts R,Marian AJdoi
10.1016/s0735-1097(01)01509-1subject
Has Abstractpub_date
2001-10-01 00:00:00pages
1175-80issue
4eissn
0735-1097issn
1558-3597pii
S0735-1097(01)01509-1journal_volume
38pub_type
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更新日期:2002-01-02 00:00:00
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更新日期:2017-09-26 00:00:00
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更新日期:2016-02-23 00:00:00
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更新日期:2005-03-15 00:00:00
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更新日期:2013-07-30 00:00:00
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更新日期:2020-05-12 00:00:00