Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis.
OBJECTIVE
We investigated the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their genes in the hearts of patients with cardiac amyloidosis and those with isolated atrial amyloidosis.


BACKGROUND
The expression of ANP and BNP is augmented in the ventricles of failing or hypertrophied hearts, or both. The expression of ANP and BNP in the ventricles of hearts with cardiac amyloidosis, which is hemodynamically similar to restrictive cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial amyloid.


METHODS
We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hybridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiac amyloidosis.


RESULTS
Four of the five right and all six left ventricular endomyocardial biopsy specimens obtained from six patients with cardiac amyloidosis were immunohistochemically 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 right atria obtained at operation showed positive immunoreactions for both peptides. Electron microscopy identified specific secretory granules in ventricular myocytes of the patients with cardiac amyloidosis, but not in ventricular myocytes from the normal control subjects. Double immunocytochemical analysis revealed the co-localization of ANP and BNP in the same granules and that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas ventricular amyloid fibrils were negative for both peptides. Both ANP mRNA and BNP mRNA were expressed in the ventricles of the patients with cardiac amyloidosis but not in the normal ventricles. The autopsy study of four patients with cardiac amyloidosis revealed an almost transmural distribution of ANP and BNP, with predominance in the endocardial side. Plasma BNP levels in the 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 augmented in the ventricular myocytes of the patients with cardiac amyloidosis. Both regional mechanical stress by amyloid deposits and hemodynamic stress by diastolic dysfunction may be responsible for the expression of the peptides in patients with cardiac amyloidosis.
Takemura
G
G
Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, Japan.
Takatsu
Y
Y
Doyama
K
K
Itoh
H
H
Saito
Y
Y
Koshiji
M
M
Ando
F
F
Fujiwara
T
T
Nakao
K
K
Fujiwara
H
H
D000368:Aged; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004699:Endocardium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006352:Heart Ventricles; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor