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.
Medical Division and EpiGen, Institute of Clinical Epidemiology and Molecular Biology, Akershus University Hospital, Lørenskog, Norway. helge.rosjo@medisin.uio.no
Helge
H
Røsjø
Cathrine
C
Husberg
Mai Britt
MB
Dahl
Mats
M
Stridsberg
Ivar
I
Sjaastad
Alexandra Vanessa
AV
Finsen
Cathrine Rein
CR
Carlson
Erik
E
Oie
Torbjørn
T
Omland
Geir
G
Christensen
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