Abstract 3735: Secretogranin II is Closely Regulated in the Murine Myocardium and Increased in the Circulation of Heart Failure Patients
Background: Secretogranin II (SgII) and chromogranin (Cg) A and B are members of the granin protein family. While CgA and B recently have been found associated with heart failure (HF) development, the regulation of SgII has not been investigated.
Aim: To examine SgII levels in the myocardium and circulation during HF development, and investigate the potential for SgII as a HF biomarker.
Methods: SgII production in the myocardium was evaluated in a post-MI HF mouse model with animals characterized by echocardiography before being sacrificed one week post-MI. Gene expression was measured with qRT-PCR, localization of SgII production examined by immunohistochemistry, and protein levels measured by RIA. In 80 HF patients recruited mainly from an outpatient HF clinic, circulating SgII levels were measured and compared to 20 age- and gender-matched healthy control subjects.
Results: Compared to sham-operated animals, SgII mRNA levels were 11.5 fold upregulated in the left ventricle (LV) (p<0.001). This was a greater relative increase than observed for LV BNP gene expression (5.8 fold increase). LV SgII protein levels were increased during HF development by 35 and 85% in the non-infarcted and infarcted region, respectively. Production of SgII in the myocardium was confined to the cardiomyocytes. SgII protein levels were unaltered in other tissues investigated (pulmonary, renal, spleen, GI-tract, and skeletal muscle). Patients with HF of mainly moderate severity had clearly increased circulating SgII levels compared to control subjects (0.17±0.01 vs. 0.12±0.01 nmol/L, p<0.001), and SgII levels were superior to CgA, an established HF biomarker, for diagnosing HF (ROC-AUC 0.84 vs. 0.61, p=0.001).
Conclusion: SgII is produced by cardiomyocytes during HF development and increased in the LV. Circulating SgII levels are also closely regulated and increased in HF patients, indicating that SgII may represent a novel cardiac biomarker.