Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C β2 activation and diabetes

Kerrie J. Way, Keiji Isshiki, Kiyoshi Suzuma, Tamotsu Yokota, Dmitriy Zvagelsky, Frederick J. Schoen, George Sandusky, Penelope A. Pechous, Chris J. Vlahos, Hisao Wakasaki, George L. King

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Protein kinase C (PKC) β isoform activity is increased in myocardium of diabetic rodents and heart failure patients. Transgenic mice overexpressing PKCβ2 (PKCβ2Tg) in the myocardium exhibit cardiomyopathy and cardiac fibrosis. In this study, we characterized the expression of connective tissue growth factor (CTGF) and transforming growth factor β (TGFβ) with the development of fibrosis in heart from PKCβ2Tg Mice at 4-16 weeks of age. Heart-to-body weight ratios of transgenic mice increased at 8 and 12 weeks, indicating hypertrophy, and ratios did not differ at 16 weeks. Collagen VI and fibronectin mRNA expression increased in PKCβ2Tg hearts at 4-12 weeks. Histological examination revealed myocyte hypertrophy, and fibrosis in 4- to 16-week PKCβ2Tg hearts. CTGF expression increased in PKCβ2Tg hearts at all ages, whereas TGFβ increased only at 8 and 12 weeks. In 8-week diabetic mouse heart, CTGF and TGFβ expression increased two- and fourfold, respectively. Similarly, CTGF expression increased in rat hearts at 2-8 weeks of diabetes. This is the first report of increased CTGF expression in myocardium of diabetic rodents suggesting that cardiac injury associated with PKCβ2 activation, diabetes, or heart failure is marked by increased CTGF expression. CTGF could act independently or together with other cytokines to induce cardiac fibrosis and dysfunction.

Original languageEnglish (US)
Pages (from-to)2709-2718
Number of pages10
JournalDiabetes
Volume51
Issue number9
StatePublished - Sep 2002
Externally publishedYes

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Connective Tissue Growth Factor
Protein Kinase C
Myocardium
Transforming Growth Factors
Fibrosis
Hypertrophy
Transgenic Mice
Rodentia
Heart Failure
Cardiomyopathies
Fibronectins
Muscle Cells
Protein Isoforms
Collagen
Body Weight
Cytokines
Messenger RNA
Wounds and Injuries

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Way, K. J., Isshiki, K., Suzuma, K., Yokota, T., Zvagelsky, D., Schoen, F. J., ... King, G. L. (2002). Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C β2 activation and diabetes. Diabetes, 51(9), 2709-2718.

Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C β2 activation and diabetes. / Way, Kerrie J.; Isshiki, Keiji; Suzuma, Kiyoshi; Yokota, Tamotsu; Zvagelsky, Dmitriy; Schoen, Frederick J.; Sandusky, George; Pechous, Penelope A.; Vlahos, Chris J.; Wakasaki, Hisao; King, George L.

In: Diabetes, Vol. 51, No. 9, 09.2002, p. 2709-2718.

Research output: Contribution to journalArticle

Way, KJ, Isshiki, K, Suzuma, K, Yokota, T, Zvagelsky, D, Schoen, FJ, Sandusky, G, Pechous, PA, Vlahos, CJ, Wakasaki, H & King, GL 2002, 'Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C β2 activation and diabetes', Diabetes, vol. 51, no. 9, pp. 2709-2718.
Way, Kerrie J. ; Isshiki, Keiji ; Suzuma, Kiyoshi ; Yokota, Tamotsu ; Zvagelsky, Dmitriy ; Schoen, Frederick J. ; Sandusky, George ; Pechous, Penelope A. ; Vlahos, Chris J. ; Wakasaki, Hisao ; King, George L. / Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C β2 activation and diabetes. In: Diabetes. 2002 ; Vol. 51, No. 9. pp. 2709-2718.
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