Aims High chromogranin-A (CgA) levels were observed inpatients with heart fai lure but its source remained uncertain. We evaluated whether CgA is produced by myocardium and might affect myocardial function. Methods and 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 get-filtration HPLC and their effects on cardiac performance assessed in isolated perfused rat heart. Ali patients showed increased CgA plasma levels (DCM 153.7 +/- 158.5 ng/mL; HCM 150.2 +/- 86.7ng/mL vs. 64.1 +/- 17.9 ng/mL of controls) with a positive correlation between CgA and left ventricular end-diastolic pressure (I)CM, 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 colocalization with BNP in all patients, but not in controls. PCR detected CgA mRNA in both pathotogic and normal myocardium, white ELISA showed a significant amount of CgA only in pathotogic myocardium (>0.5 mu g/g of tissue); get-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. Conclusion 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.

Myocardial production of chromogranin A in human heart: a new regulatory peptide of cardiac function

CORTI , ANGELO;
2007

Abstract

Aims High chromogranin-A (CgA) levels were observed inpatients with heart fai lure but its source remained uncertain. We evaluated whether CgA is produced by myocardium and might affect myocardial function. Methods and 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 get-filtration HPLC and their effects on cardiac performance assessed in isolated perfused rat heart. Ali patients showed increased CgA plasma levels (DCM 153.7 +/- 158.5 ng/mL; HCM 150.2 +/- 86.7ng/mL vs. 64.1 +/- 17.9 ng/mL of controls) with a positive correlation between CgA and left ventricular end-diastolic pressure (I)CM, 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 colocalization with BNP in all patients, but not in controls. PCR detected CgA mRNA in both pathotogic and normal myocardium, white ELISA showed a significant amount of CgA only in pathotogic myocardium (>0.5 mu g/g of tissue); get-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. Conclusion 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/7904
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