Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure

Xian Wu Cheng, Koji Obata, Masafumi Kuzuya, Hideo Izawa, Kae Nakamura, Eri Asai, Tetsuro Nagasaka, Masako Saka, Takahiro Kimata, Akiko Noda, Kohzo Nagata, Hai Jin, Guo Ping Shi, Akihisa Iguchi, Toyoaki Murohara, Mitsuhiro Yokota

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Cathepsins are cysteine proteases that participate in various types of tissue remodeling. However, their expressions during myocardial remodeling have not been examined. In this study, we investigated their expressions in the left ventricular (LV) myocardium of rats and humans with hypertension-induced LV hypertrophy or heart failure (HF). Real-time PCR and immunoblot analysis revealed that the abundance of cathepsin S mRNA or protein in the LV tissues was greater in rats or humans with HF than in those with hypertrophy or in control subjects. Immunostaining showed that cathepsin S was localized predominantly to cardiac myocytes and coronary vascular smooth muscle cells, but also overlapped in part with macrophages. Elastic lamina fragmentations significantly increased in the LV intramyocardial coronary arteries of HF rats. The amount of elastolytic activity in the extract of the LV myocardium was markedly increased for HF rats compared with controls, and this activity was mostly because of cathepsin S. Although the amount of elastin mRNA was increased in the LV myocardium of HF rats, the area of interstitial elastin was not. The expression of interleukin 1β was increased in the LV myocardium of HF rats, and this cytokine was found to increase the expression and activity of cathepsin S in cultured neonatal cardiomyocytes. These results suggest that cathepsin S participates in pathological LV remodeling associated with hypertension-induced HF. This protease is, thus, a potential target for therapeutics aimed at preventing or reversing cardiac remodeling.

Original languageEnglish
Pages (from-to)979-987
Number of pages9
JournalHypertension
Volume48
Issue number5
DOIs
Publication statusPublished - 01-11-2006
Externally publishedYes

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cathepsin S
Cathepsins
Myocardium
Heart Failure
Elastin
Cardiac Myocytes
Hypertension
Messenger RNA
Ventricular Remodeling
Cysteine Proteases
Left Ventricular Hypertrophy
Interleukin-1
Vascular Smooth Muscle
Hypertrophy
Smooth Muscle Myocytes
Real-Time Polymerase Chain Reaction
Coronary Vessels
Peptide Hydrolases
Macrophages
Cytokines

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Cheng, Xian Wu ; Obata, Koji ; Kuzuya, Masafumi ; Izawa, Hideo ; Nakamura, Kae ; Asai, Eri ; Nagasaka, Tetsuro ; Saka, Masako ; Kimata, Takahiro ; Noda, Akiko ; Nagata, Kohzo ; Jin, Hai ; Shi, Guo Ping ; Iguchi, Akihisa ; Murohara, Toyoaki ; Yokota, Mitsuhiro. / Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure. In: Hypertension. 2006 ; Vol. 48, No. 5. pp. 979-987.
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abstract = "Cathepsins are cysteine proteases that participate in various types of tissue remodeling. However, their expressions during myocardial remodeling have not been examined. In this study, we investigated their expressions in the left ventricular (LV) myocardium of rats and humans with hypertension-induced LV hypertrophy or heart failure (HF). Real-time PCR and immunoblot analysis revealed that the abundance of cathepsin S mRNA or protein in the LV tissues was greater in rats or humans with HF than in those with hypertrophy or in control subjects. Immunostaining showed that cathepsin S was localized predominantly to cardiac myocytes and coronary vascular smooth muscle cells, but also overlapped in part with macrophages. Elastic lamina fragmentations significantly increased in the LV intramyocardial coronary arteries of HF rats. The amount of elastolytic activity in the extract of the LV myocardium was markedly increased for HF rats compared with controls, and this activity was mostly because of cathepsin S. Although the amount of elastin mRNA was increased in the LV myocardium of HF rats, the area of interstitial elastin was not. The expression of interleukin 1β was increased in the LV myocardium of HF rats, and this cytokine was found to increase the expression and activity of cathepsin S in cultured neonatal cardiomyocytes. These results suggest that cathepsin S participates in pathological LV remodeling associated with hypertension-induced HF. This protease is, thus, a potential target for therapeutics aimed at preventing or reversing cardiac remodeling.",
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Cheng, XW, Obata, K, Kuzuya, M, Izawa, H, Nakamura, K, Asai, E, Nagasaka, T, Saka, M, Kimata, T, Noda, A, Nagata, K, Jin, H, Shi, GP, Iguchi, A, Murohara, T & Yokota, M 2006, 'Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure', Hypertension, vol. 48, no. 5, pp. 979-987. https://doi.org/10.1161/01.HYP.0000242331.99369.2f

Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure. / Cheng, Xian Wu; Obata, Koji; Kuzuya, Masafumi; Izawa, Hideo; Nakamura, Kae; Asai, Eri; Nagasaka, Tetsuro; Saka, Masako; Kimata, Takahiro; Noda, Akiko; Nagata, Kohzo; Jin, Hai; Shi, Guo Ping; Iguchi, Akihisa; Murohara, Toyoaki; Yokota, Mitsuhiro.

In: Hypertension, Vol. 48, No. 5, 01.11.2006, p. 979-987.

Research output: Contribution to journalArticle

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T1 - Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure

AU - Cheng, Xian Wu

AU - Obata, Koji

AU - Kuzuya, Masafumi

AU - Izawa, Hideo

AU - Nakamura, Kae

AU - Asai, Eri

AU - Nagasaka, Tetsuro

AU - Saka, Masako

AU - Kimata, Takahiro

AU - Noda, Akiko

AU - Nagata, Kohzo

AU - Jin, Hai

AU - Shi, Guo Ping

AU - Iguchi, Akihisa

AU - Murohara, Toyoaki

AU - Yokota, Mitsuhiro

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Cathepsins are cysteine proteases that participate in various types of tissue remodeling. However, their expressions during myocardial remodeling have not been examined. In this study, we investigated their expressions in the left ventricular (LV) myocardium of rats and humans with hypertension-induced LV hypertrophy or heart failure (HF). Real-time PCR and immunoblot analysis revealed that the abundance of cathepsin S mRNA or protein in the LV tissues was greater in rats or humans with HF than in those with hypertrophy or in control subjects. Immunostaining showed that cathepsin S was localized predominantly to cardiac myocytes and coronary vascular smooth muscle cells, but also overlapped in part with macrophages. Elastic lamina fragmentations significantly increased in the LV intramyocardial coronary arteries of HF rats. The amount of elastolytic activity in the extract of the LV myocardium was markedly increased for HF rats compared with controls, and this activity was mostly because of cathepsin S. Although the amount of elastin mRNA was increased in the LV myocardium of HF rats, the area of interstitial elastin was not. The expression of interleukin 1β was increased in the LV myocardium of HF rats, and this cytokine was found to increase the expression and activity of cathepsin S in cultured neonatal cardiomyocytes. These results suggest that cathepsin S participates in pathological LV remodeling associated with hypertension-induced HF. This protease is, thus, a potential target for therapeutics aimed at preventing or reversing cardiac remodeling.

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