Cellular localization and structural characterization of natriuretic peptide-expressing ventricular myocytes from patients with dilated cardiomyopathy.

Abstract

Although atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are expressed in the tissue of ventricles of failing hearts, the localization and histopathological features of natriuretic peptide-expressing ventricular myocytes have not been clearly described. This study was designed to characterize the ventricular cardiomyocytes that express both natriuretic peptides in 19 patients with dilated cardiomyopathy (DCM). Immunohistochemistry and in situ hybridization for ANP and BNP were performed with left ventricular biopsy specimens. Peptide-expressing myocytes were examined by hematoxylin-eosin staining and desmin immunohistochemistry and by in situ hybridization to characterize the corresponding cells histopathologically. The distribution of ANP- and BNP-expressing myocytes in the ventricle was identical and was located in the subendocardial layer, fibrous area, and perivascular region. Desmin was found in heavy deposits in the cytosol of peptide-expressing myocytes, and desmin mRNA was not always augmented in the peptide-expressing myocytes. These results indicate that the augmented expression of natriuretic peptides in the left ventricle of patients with DCM is not due solely to global stress on the ventricular wall but is also influenced by regional conditions and is associated with structural changes in the myocytes.

Loss of the Normal Epicardial to Endocardial Gradient of cftr mRNA Expression in the Hypertrophied Rabbit Left Ventricle

“…The increase in anf mRNA expression in subendocardial and perivascular regions is similar to that reported for spontaneous biventricular hypertrophy in the rat [15] and in patients with dilated cardiomyopathy [25]. The variable increase in anf mRNA expression we observed is also similar to that reported by Vikstrom et al in a transgenic mouse model of hypertrophic cardiomyopathy [26].…”

Immunohistochemistry of Atrial and Brain Natriuretic Peptides in Control Cats and Cats with Hypertrophic Cardiomyopathy

“…Similar findings are reported in healthy pig and human atria, 16,35,37 and in abnormal ventricles in dogs. 7 Presumably, this pattern of distribution developed to facilitate endocardial release of the peptide after myocardial production.…”

“…The presence of ventricular BNP has been observed previously in several cardiac diseases, including myocarditis, 35 myocardial infarction, 5 amyloidosis, 36 chronic heart failure, 17 dilated cardiomyopathy, 37 and HCM. 20,34 Tissue expression of ANP and BNP can correlate to their plasma levels, as reported previously.…”

“…5,18,21,40 Minute amounts of BNP were found in ventricle of dogs, 2 and its localization in humans is still controversial. 15,20,37 These inconsistencies in many species may result from differences in sensitivity of immunohistochemistry to the uneven tissue distribution of the peptide (demonstrated as a layered pattern with higher concentration at the endocardial side), to different affinities of the antibodies used, or to a variability in distribution of BNP in those species.…”

Intramyocardial BNP Gene Delivery Improves Cardiac Function Through Distinct Context-Dependent Mechanisms

“…32 Further, in primary cultures of neonatal rat cardiac fibroblasts, in which both GG-A and GC-B are expressed, porcine BNP-32 (structure very similar to hBNP-32) inhibited growth factor-dependent-3 Hthymidine incorporation, this effect being enhanced by phosphodiesterase inhibition. 31 Interestingly, some BNP-containing granules were noted in ventricles after overexpression of BNP, whereas staining was diffuse in LacZ-injected hearts, suggesting that if tissue BNP concentration is high, as in patients with dilated cardiomyopathy, 33 BNP is stored to some extent in granules.…”