title: Myocardial production of chromogranin A in human heart: a new regulatory peptide of cardiac function.
abstract: OBJECTIVE
  High chromogranin-A (CgA) levels were observed in patients with heart failure but its source remained uncertain. We evaluated whether CgA is produced by myocardium and might affect myocardial function.
  
  
  RESULTS
  We measured plasma CgA levels and performed immunohistochemistry with anti-CgA antibodies on myocardial biopsies in 40 patients with dilated cardiomyopathy (DCM) and 20 patients with hypertrophic cardiomyopathy (HCM). Surgical myocardial specimens from DCM and HCM patients were used for PCR and ELISA. The presence of CgA-derived fragments in plasma was evaluated by gel-filtration HPLC and their effects on cardiac performance assessed in isolated perfused rat heart. All patients showed increased CgA plasma levels (DCM 153.7 +/- 158.5 ng/mL; HCM 150.2 +/- 86.7 ng/mL vs. 64.1 +/- 17.9 ng/mL of controls) with a positive correlation between CgA and left ventricular end-diastolic pressure (DCM, R = 0.86; HCM, R = 0.83), and plasma brain natriuretic peptide (BNP) levels (DCM, R = 0.88; HCM, R = 0.85) (P < 0.001). Immunohistochemistry showed cytoplasmic expression of CgA and co-localization with BNP in all patients, but not in controls. PCR detected CgA mRNA in both pathologic and normal myocardium, while ELISA showed a significant amount of CgA only in pathologic myocardium (>0.5 microg/g of tissue); gel-filtration HPLC of plasma samples identified immunoreactive N-terminal CgA fragments containing vasostatin-1. Administration of vasostatin-1 to perfused rat heart produced negative inotropic and lusitropic effects counteracting isoproterenol actions.
  
  
  CONCLUSIONS
  We demonstrate for the first time that CgA is produced by human myocardium and exerts negative inotropic and lusitropic effects on mammalian heart. CgA may represent a key player in neuroendocrine regulation of cardiac function and a potential therapeutic target in heart failure.
authors: Cardiology Department, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy. mauriziopieroni@yahoo.com
authors: Maurizio
authors: M
authors: Pieroni
authors: Angelo
authors: A
authors: Corti
authors: Bruno
authors: B
authors: Tota
authors: Flavio
authors: F
authors: Curnis
authors: Tommaso
authors: T
authors: Angelone
authors: Barbara
authors: B
authors: Colombo
authors: Maria Carmela
authors: MC
authors: Cerra
authors: Fulvio
authors: F
authors: Bellocci
authors: Filippo
authors: F
authors: Crea
authors: Attilio
authors: A
authors: Maseri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis*; D053379:Chromogranin A / Q000378:metabolism* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D053379:Chromogranin A; D010446:Peptide Fragments; C064110:vasostatin I