EXPRESSION OF ATRIAL AND BRAIN NATRIURETIC PEPTIDES AND THEIR GENES IN HEARTS OF PATIENTS WITH CARDIAC AMYLOIDOSIS

Objectives. We investigated the expression of atrial natriuretic pepti de (ANP) and brain natriuretic peptide (BNP) and their genes in the he arts of patients with cardiac amyloidosis and those with isolated atri al amyloidosis. Background. The expression of ANP and BNP is augmented in the ventricles of failing or hypertrophied hearts, or both. The ex pression of ANP and BNP in the ventricles of hearts with cardiac amylo idosis, which is hemodynamically similar to restrictive cardiomyopathy , is not yet known. ANP is the precursor protein of isolated atrial am yloid. Methods. We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hyb ridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiac amyloidosis. Results. Four of the five r ight and all six left ventricular endomyocardial biopsy specimens obta ined from six patients with cardiac amyloidosis were immunohistochemic ally positive for both ANP and BNP; none of the biopsy specimens from eight normal subjects were positive for ANP or BNP. All four of the ri ght atria obtained at operation showed positive immunoreactions for bo th peptides. Electron microscopy identified specific secretory granule s in ventricular myoctyes of the patients with cardiac amyloidosis, bu t not in ventricular myocytes from the normal control subjects. Double immunocytochemical analysis revealed the co localization of ANP and B NP in the same granules and that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas ventricular amyloid fibrils we re negative for both peptides. Both ANP mRNA and BNP mRNA were express ed in the ventricles of the patients with cardiac amyloidosis but not in the normal ventricles. The autopsy study of four patients with card iac amyloidosis revealed an almost transmural distribution of ANP and BNP, with predominance in the endocardial side. Plasma BNP levels in t he patients were markedly elevated ([mean +/- SD] 1,165.1 +/- 561.2 pg /ml) compared with those in the control subjects (8.9 +/- 6.0 pg/ml, p < 0.05). Conclusions. Expression of ANP and BNP and their genes was a ugmented in the ventricular myocytes of the patients with cardiac amyl oidosis. Both regional mechanical stress by amyloid deposits and hemod ynamic stress by diastolic dysfunction may be responsible for the expr ession of the peptides in patients with cardiac amyloidosis. (C) 1998 by the American College of Cardiology.