Chromogranin B in heart failure: a putative cardiac biomarker expressed in the failing myocardium.
BACKGROUND
Chromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development.


RESULTS
CgB regulation was investigated in patients with chronic HF and in a post-myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5.2-fold increased in the noninfarcted part of the left ventricle of HF animals compared with sham-operated animals (P<0.001). CgB mRNA level in HF animals correlated closely with animal lung weight (r=0.74, P=0.04) but not with CgA mRNA levels (r=0.20, P=0.61). CgB protein levels were markedly increased in both the noninfarcted (110%) and the infarcted part of the left ventricle (70%) but unaltered in other tissues investigated. Myocardial CgB immunoreactivity was confined to cardiomyocytes. Norepinephrine, angiotensin II, and transforming growth factor-beta increased CgB gene expression in cardiomyocytes. Circulating CgB levels were increased in HF animals (median levels in HF animals versus sham, 1.23 [interquartile range, 1.03 to 1.93] versus 0.98 [0.90 to 1.04] nmol/L; P=0.003) and in HF patients (HF patients versus control, 1.66 [1.48 to 1.85] versus 1.47 [1.39 to 1.58] nmol/L; P=0.007), with levels increasing in proportion to New York Heart Association functional class (P=0.03 for trend). Circulating CgB levels were only modestly correlated with CgA (r=0.31, P=0.009) and B-type natriuretic peptide levels (r=0.27, P=0.014).


CONCLUSIONS
CgB production is increased and regulated in proportion to disease severity in the left ventricle and circulation during HF development.
Røsjø
Helge
H
Medical Division and EpiGen, Institute of Clinical Epidemiology and Molecular Biology, Akershus University Hospital, Lørenskog, Norway. helge.rosjo@medisin.uio.no
Husberg
Cathrine
C
Dahl
Mai Britt
MB
Stridsberg
Mats
M
Sjaastad
Ivar
I
Finsen
Alexandra Vanessa
AV
Carlson
Cathrine Rein
CR
Oie
Erik
E
Omland
Torbjørn
T
Christensen
Geir
G
D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000503:physiopathology; D016022:Case-Control Studies; D053378:Chromogranin B / Q000097:blood*; D004195:Disease Models, Animal; D018450:Disease Progression; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000473:pathology; D006334:Heart Function Tests; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011336:Probability; D011863:Radioimmunoassay; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D015415:Biomarkers; D053378:Chromogranin B