Medical Division and EpiGen, Institute of Clinical Epidemiology and Molecular Biology, Akershus University Hospital, Lørenskog, Norway.
Circ Heart Fail. 2010 Jul;3(4):503-11. doi: 10.1161/CIRCHEARTFAILURE.109.867747. Epub 2010 Jun 2.
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.
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).
CgB production is increased and regulated in proportion to disease severity in the left ventricle and circulation during HF development.
嗜铬粒蛋白 B（CgB）是颗粒蛋白家族的成员。由于 CgB 常与最近发现的心脏生物标志物嗜铬粒蛋白 A（CgA）共定位，因此我们假设 CgB 在心力衰竭（HF）发展过程中受到调节。
在慢性 HF 患者和心肌梗死后 HF 小鼠模型中研究了 CgB 的调节。通过超声心动图对动物进行表型特征描述，并在心肌梗死后 1 周处死动物。与假手术动物相比，HF 动物左心室未梗死部分的 CgB mRNA 水平增加了 5.2 倍（P<0.001）。HF 动物的 CgB mRNA 水平与动物肺重密切相关（r=0.74，P=0.04），但与 CgA mRNA 水平无关（r=0.20，P=0.61）。CgB 蛋白水平在未梗死（110%）和左心室梗死部分（70%）均显著增加，但在其他研究的组织中未改变。心肌 CgB 免疫反应性仅限于心肌细胞。去甲肾上腺素、血管紧张素 II 和转化生长因子-β增加了心肌细胞中的 CgB 基因表达。HF 动物的循环 CgB 水平升高（HF 动物的中位数水平与假手术动物相比，1.23[四分位间距，1.03 至 1.93]与 0.98[0.90 至 1.04]nmol/L；P=0.003），HF 患者与对照相比，1.66[1.48 至 1.85]与 1.47[1.39 至 1.58]nmol/L；P=0.007），并且随着纽约心脏协会功能分类的增加而增加（趋势 P=0.03）。循环 CgB 水平与 CgA（r=0.31，P=0.009）和 B 型利钠肽水平（r=0.27，P=0.014）仅中度相关。
在 HF 发展过程中，CgB 的产生与左心室和循环中的疾病严重程度成比例增加并受到调节。
