Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy: Evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes

Masaki Harada, Hiroshi Itoh, Osamu Nakagawa, Yoshihiro Ogawa, Yoshihiro Miyamoto, Koichiro Kuwahara, Emiko Ogawa, Toshio Igaki, Jun Yamashita, Izuru Masuda, Takaaki Yoshimasa, Issei Tanaka, Yoshihiko Saito, Kazuwa Nakao

Research output: Contribution to journalArticle

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Abstract

Background: In cardiac hypertrophy, both excessive enlargement of cardiac myocytes and progressive interstitial fibrosis are well known to occur simultaneously. In the present study, to investigate the interaction between ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs), mostly fibroblasts, during cardiocytes hypertrophy, we examined the change in cell size and gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cultured MCs as markers for hypertrophy in the neonatal rat ventricular cardiac cell culture system. Methods and Results: The size of cultured MCs significantly increased in the MC-NMC coculture. Concomitantly, secretions of ANP and BNP into culture media were significantly increased in the MC-NMC coculture compared with in the MC culture (with the possible contamination of NMC <1% of MC). Moreover, in the MC culture, enlargement of MC and an increase in ANP and BNP secretions were induced by treatment with conditioned media of the NMC culture. A considerable amount of endothelin (ET)-1 production was detected in the NMC- conditioned media. BQ-123, an ET-A receptor antagonist, and bosentan, a nonselective ET receptor antagonist, significantly blocked the hypertrophic response of MCs induced by treatment with NMC-conditioned media. Angiotensin II (Ang II) (10-10 to 10-6 mol/L) and transforming growth factor-β1 (TGF-β1) (10-13 to 10-9 mol/L), both of which are known to be cardiac hypertrophic factors, did not induce hypertrophy in MC culture, but both Ang II and TGF-β1 increased the size of MCs and augmented ANP and BNP productions in the MC-NMC coculture. This hypertrophic activity of Ang II and TGF-β1 was associated with the potentiation of ET-1 production in the MC- NMC coculture, and the effect of Ang II or TGF-β1 on the secretions of ANP and BNP in the coculture was significantly suppressed by pretreatment with BQ-123. Conclusions: These results demonstrate that NMCs regulate MC hypertrophy at least partially via ET-1 secretion and that the interaction between MCs and NMCs plays a critical role during the process of Ang II-or TGF-β1-induced cardiocyte hypertrophy.

Original languageEnglish
Pages (from-to)3737-3744
Number of pages8
JournalCirculation
Volume96
Issue number10
DOIs
Publication statusPublished - Nov 18 1997

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Endothelin-1
Muscle Cells
Hypertrophy
Brain Natriuretic Peptide
Transforming Growth Factors
Atrial Natriuretic Factor
Coculture Techniques
Angiotensin II
Conditioned Culture Medium
Cardiac Myocytes
Cardiomegaly
Cell Size
Culture Media

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy : Evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes. / Harada, Masaki; Itoh, Hiroshi; Nakagawa, Osamu; Ogawa, Yoshihiro; Miyamoto, Yoshihiro; Kuwahara, Koichiro; Ogawa, Emiko; Igaki, Toshio; Yamashita, Jun; Masuda, Izuru; Yoshimasa, Takaaki; Tanaka, Issei; Saito, Yoshihiko; Nakao, Kazuwa.

In: Circulation, Vol. 96, No. 10, 18.11.1997, p. 3737-3744.

Research output: Contribution to journalArticle

Harada, M, Itoh, H, Nakagawa, O, Ogawa, Y, Miyamoto, Y, Kuwahara, K, Ogawa, E, Igaki, T, Yamashita, J, Masuda, I, Yoshimasa, T, Tanaka, I, Saito, Y & Nakao, K 1997, 'Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy: Evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes', Circulation, vol. 96, no. 10, pp. 3737-3744. https://doi.org/10.1161/01.CIR.96.10.3737
Harada, Masaki ; Itoh, Hiroshi ; Nakagawa, Osamu ; Ogawa, Yoshihiro ; Miyamoto, Yoshihiro ; Kuwahara, Koichiro ; Ogawa, Emiko ; Igaki, Toshio ; Yamashita, Jun ; Masuda, Izuru ; Yoshimasa, Takaaki ; Tanaka, Issei ; Saito, Yoshihiko ; Nakao, Kazuwa. / Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy : Evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes. In: Circulation. 1997 ; Vol. 96, No. 10. pp. 3737-3744.
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abstract = "Background: In cardiac hypertrophy, both excessive enlargement of cardiac myocytes and progressive interstitial fibrosis are well known to occur simultaneously. In the present study, to investigate the interaction between ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs), mostly fibroblasts, during cardiocytes hypertrophy, we examined the change in cell size and gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cultured MCs as markers for hypertrophy in the neonatal rat ventricular cardiac cell culture system. Methods and Results: The size of cultured MCs significantly increased in the MC-NMC coculture. Concomitantly, secretions of ANP and BNP into culture media were significantly increased in the MC-NMC coculture compared with in the MC culture (with the possible contamination of NMC <1{\%} of MC). Moreover, in the MC culture, enlargement of MC and an increase in ANP and BNP secretions were induced by treatment with conditioned media of the NMC culture. A considerable amount of endothelin (ET)-1 production was detected in the NMC- conditioned media. BQ-123, an ET-A receptor antagonist, and bosentan, a nonselective ET receptor antagonist, significantly blocked the hypertrophic response of MCs induced by treatment with NMC-conditioned media. Angiotensin II (Ang II) (10-10 to 10-6 mol/L) and transforming growth factor-β1 (TGF-β1) (10-13 to 10-9 mol/L), both of which are known to be cardiac hypertrophic factors, did not induce hypertrophy in MC culture, but both Ang II and TGF-β1 increased the size of MCs and augmented ANP and BNP productions in the MC-NMC coculture. This hypertrophic activity of Ang II and TGF-β1 was associated with the potentiation of ET-1 production in the MC- NMC coculture, and the effect of Ang II or TGF-β1 on the secretions of ANP and BNP in the coculture was significantly suppressed by pretreatment with BQ-123. Conclusions: These results demonstrate that NMCs regulate MC hypertrophy at least partially via ET-1 secretion and that the interaction between MCs and NMCs plays a critical role during the process of Ang II-or TGF-β1-induced cardiocyte hypertrophy.",
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T1 - Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy

T2 - Evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes

AU - Harada, Masaki

AU - Itoh, Hiroshi

AU - Nakagawa, Osamu

AU - Ogawa, Yoshihiro

AU - Miyamoto, Yoshihiro

AU - Kuwahara, Koichiro

AU - Ogawa, Emiko

AU - Igaki, Toshio

AU - Yamashita, Jun

AU - Masuda, Izuru

AU - Yoshimasa, Takaaki

AU - Tanaka, Issei

AU - Saito, Yoshihiko

AU - Nakao, Kazuwa

PY - 1997/11/18

Y1 - 1997/11/18

N2 - Background: In cardiac hypertrophy, both excessive enlargement of cardiac myocytes and progressive interstitial fibrosis are well known to occur simultaneously. In the present study, to investigate the interaction between ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs), mostly fibroblasts, during cardiocytes hypertrophy, we examined the change in cell size and gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cultured MCs as markers for hypertrophy in the neonatal rat ventricular cardiac cell culture system. Methods and Results: The size of cultured MCs significantly increased in the MC-NMC coculture. Concomitantly, secretions of ANP and BNP into culture media were significantly increased in the MC-NMC coculture compared with in the MC culture (with the possible contamination of NMC <1% of MC). Moreover, in the MC culture, enlargement of MC and an increase in ANP and BNP secretions were induced by treatment with conditioned media of the NMC culture. A considerable amount of endothelin (ET)-1 production was detected in the NMC- conditioned media. BQ-123, an ET-A receptor antagonist, and bosentan, a nonselective ET receptor antagonist, significantly blocked the hypertrophic response of MCs induced by treatment with NMC-conditioned media. Angiotensin II (Ang II) (10-10 to 10-6 mol/L) and transforming growth factor-β1 (TGF-β1) (10-13 to 10-9 mol/L), both of which are known to be cardiac hypertrophic factors, did not induce hypertrophy in MC culture, but both Ang II and TGF-β1 increased the size of MCs and augmented ANP and BNP productions in the MC-NMC coculture. This hypertrophic activity of Ang II and TGF-β1 was associated with the potentiation of ET-1 production in the MC- NMC coculture, and the effect of Ang II or TGF-β1 on the secretions of ANP and BNP in the coculture was significantly suppressed by pretreatment with BQ-123. Conclusions: These results demonstrate that NMCs regulate MC hypertrophy at least partially via ET-1 secretion and that the interaction between MCs and NMCs plays a critical role during the process of Ang II-or TGF-β1-induced cardiocyte hypertrophy.

AB - Background: In cardiac hypertrophy, both excessive enlargement of cardiac myocytes and progressive interstitial fibrosis are well known to occur simultaneously. In the present study, to investigate the interaction between ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs), mostly fibroblasts, during cardiocytes hypertrophy, we examined the change in cell size and gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cultured MCs as markers for hypertrophy in the neonatal rat ventricular cardiac cell culture system. Methods and Results: The size of cultured MCs significantly increased in the MC-NMC coculture. Concomitantly, secretions of ANP and BNP into culture media were significantly increased in the MC-NMC coculture compared with in the MC culture (with the possible contamination of NMC <1% of MC). Moreover, in the MC culture, enlargement of MC and an increase in ANP and BNP secretions were induced by treatment with conditioned media of the NMC culture. A considerable amount of endothelin (ET)-1 production was detected in the NMC- conditioned media. BQ-123, an ET-A receptor antagonist, and bosentan, a nonselective ET receptor antagonist, significantly blocked the hypertrophic response of MCs induced by treatment with NMC-conditioned media. Angiotensin II (Ang II) (10-10 to 10-6 mol/L) and transforming growth factor-β1 (TGF-β1) (10-13 to 10-9 mol/L), both of which are known to be cardiac hypertrophic factors, did not induce hypertrophy in MC culture, but both Ang II and TGF-β1 increased the size of MCs and augmented ANP and BNP productions in the MC-NMC coculture. This hypertrophic activity of Ang II and TGF-β1 was associated with the potentiation of ET-1 production in the MC- NMC coculture, and the effect of Ang II or TGF-β1 on the secretions of ANP and BNP in the coculture was significantly suppressed by pretreatment with BQ-123. Conclusions: These results demonstrate that NMCs regulate MC hypertrophy at least partially via ET-1 secretion and that the interaction between MCs and NMCs plays a critical role during the process of Ang II-or TGF-β1-induced cardiocyte hypertrophy.

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