title: Atrial natriuretic peptide and osteopontin are useful markers of cardiac disorders in mice.
abstract: Biomarkers are not established for cardiovascular phenotyping in mice. We compared the use of echocardiography with the determination of N-terminal propeptide of the atrial natriuretic peptide (Nt-proANP) and osteopontin (Opn). We measured plasma Nt-proANP and Opn levels in (1) the inbred strains C57BL/6, BALB/c, C3H/He, DBA/2, FVB/N, 129S1/Sv; (2) a surgical model of nonischemic myocardial infarction; and (3) delta-sarcoglycan (Sgcd) and calsarcin 1 [also known as myozenin 2 (Myoz2)] knockout models of cardiomyopathy. Left ventricular function was assessed as fractional shortening (FS) by echocardiography in conscious mice. Plasma Nt-proANP exhibited marked variability and ranged from 0.31 +/- 0.19 (C57BL/6 male mice) to 1.34 +/- 0.43 nmol/l (DBA/2 female mice), depending on sex, age, and genetic background. Opn was less variable than Nt-proANP and was decreased significantly in C3H/He and DBA/2 throughout the 16 wk of study. Nt-proANP increased temporarily in mice with myocardial injury. In contrast, Opn increased in both operated and sham-treated mice. Nt-proANP was inversely correlated with FS and distinguished controls from Sgcd and Myoz2 mutants with 100% sensitivity and 71% specificity. Opn was increased in Sgcd mutants, which exhibited only mildly reduced FS but marked myocardial degeneration and fibrosis. Both of these histologic features were absent in Myoz2 mutants. Nt-proANP is an early marker of cardiac disease and is suitable for age- and sex-matched comparisons between groups of transgenic and matched control mice. Opn is useful to detect inflammatory and degenerative myocardial disorders that may be missed by echocardiography.
authors.affiliation: Department of Medicine III, Otto-Meyerhof-Zentrum, University of Heidelberg, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schoensiegel
authors.forename: Raffi
authors.initials: R
authors.lastname: Bekeredjian
authors.forename: Anja
authors.initials: A
authors.lastname: Schrewe
authors.forename: Dieter
authors.initials: D
authors.lastname: Weichenhan
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Boris T
authors.initials: BT
authors.lastname: Ivandic
mesh_terms: D000375:Aging / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006331:Heart Diseases / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D053495:Osteopontin / Q000097:blood*; D010641:Phenotype; D049031:Sarcoglycans / Q000172:deficiency / Q000235:genetics; D013045:Species Specificity; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C523646:Myoz2 protein, mouse; D049031:Sarcoglycans; C506896:Spp1 protein, mouse; D053495:Osteopontin; D009320:Atrial Natriuretic Factor