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Impaired cardiac contraction and relaxation and decreased expression of sarcoplasmic Ca 2+ ‐ATPase in mice lacking the CREM gene
Author(s) -
Müller Frank U.,
Lewin Geertje,
Matus Marek,
Neumann Joachim,
Riemann Burkhard,
Wistuba Joachim,
Schütz Günther,
Schmitz Wilhelm
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0486fje
Subject(s) - medicine , endocrinology , heart failure , cardiac function curve , serca , phospholamban , biology , contraction (grammar) , endoplasmic reticulum , microbiology and biotechnology , atpase , biochemistry , enzyme
Congestive heart failure is the common endpoint of various cardiac diseases representing a leading cause of cardiovascular mortality in Western countries. Characteristic functional alterations of the failing heart are explained by expressional changes of myocardial regulatory proteins; however, little is known about underlying mechanisms regulating cardiac gene expression in the failing heart. Here, we address the specific role of transcription factor CREM for cardiac function in CREM mutant mice with complete inactivation of the CREM gene. We show that CREM mutant mice display distinct alterations of cardiac function resembling characteristic functional defects of the failing heart. Left ventricular hemodynamic assessment of CREM mutant mice revealed impairment of both cardiac contraction and relaxation in basal state, as well as a decreased responsiveness to β‐adrenergic stimulation. The diminished cardiac contractile performance was associated with a selective down‐regulation of β 1 ‐adrenergic 2+ receptors and a decreased ventricular expression of SERCA, the Ca‐ATPase of the sarcoplasmic reticulum. The cardiac phenotype of CREM mutant mice provides the first evidence that CREM represents an important key regulator of cardiac gene expression, which is essential for normal left ventricular contractile performance and response to β‐adrenoreceptor stimulation.