Cardiac fibrosis in mice lacking brain natriuretic peptide

Naohisa Tamura, Yoshihiro Ogawa, Hideki Chusho, Kenji Nakamura, Kazuki Nakao, Michio Suda, Masato Kasahara, Ryuju Hashimoto, Goro Katsuura, Masashi Mukoyama, Hiroshi Itoh, Yoshihiko Saito, Issei Tanaka, Hiroki Otani, Motoya Katsuki, Kazuwa Nakao

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Abstract

Cardiac fibrosis, defined as a proliferation of interstitial fibroblasts and biosynthesis of extracellular matrix components in the ventricles of the heart, is a consequence of remodeling processes initiated by pathologic events associated with a variety of cardiovascular disorders, which leads to abnormal myocardial stiffness and, ultimately, ventricular dysfunction. Brain natriuretic peptide (BNP) is a cardiac hormone produced primarily by ventricular myocytes, and its plasma concentrations are markedly elevated in patients with congestive heart failure and acute myocardial infarction. However, its precise functional significance has been undefined. In this paper, we report the generation of mice with targeted disruption of BNP (Nppb(-/-) mice). We observed multifocal fibrotic lesions in the ventricles from Nppb(-/-) mice. No signs of systemic hypertension and ventricular hypertrophy are noted in Nppb(-/-) mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in Nppb(-/- ) mice, whereas no focal fibrotic changes are found in wild-type littermates (Nppb(+/+) mice). This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides evidence for its role as a local regulator of ventricular remodeling.

Original languageEnglish
Pages (from-to)4239-4244
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number8
DOIs
Publication statusPublished - 2000 Apr 11

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    Tamura, N., Ogawa, Y., Chusho, H., Nakamura, K., Nakao, K., Suda, M., Kasahara, M., Hashimoto, R., Katsuura, G., Mukoyama, M., Itoh, H., Saito, Y., Tanaka, I., Otani, H., Katsuki, M., & Nakao, K. (2000). Cardiac fibrosis in mice lacking brain natriuretic peptide. Proceedings of the National Academy of Sciences of the United States of America, 97(8), 4239-4244. https://doi.org/10.1073/pnas.070371497