Hemodynamic regulation of tumor necrosis factor-α gene and protein expression in adult feline myocardium

Samir R. Kapadia, Hakan Oral, Joseph Lee, Masayuki Nakano, George Taffet, Douglas L. Mann

Research output: Contribution to journalArticle

253 Scopus citations

Abstract

Tumor necrosis factor-α (TNF-α) mRNA and protein biosynthesis were examined in adult feline myocardium in the presence and absence of superimposed hemodynamic pressure overloading. A brief period of hemodynamic pressure overloading ex vive resulted in de novo TNF-α mRNA expression within 30 minutes and de novo TNF-α protein production within 60 minutes; neither TNF-α mRNA nor protein was detected in hearts perfused at normal perfusion pressures. Moreover, TNF-α mRNA and protein biosynthesis were observed in myocyte and nonmyocyte cell types in the pressure-overloaded hearts. To determine whether a simple passive stretch of the myocardium was a sufficient stimulus for TNF-α biosynthesis, we examined TNF-α mRNA expression in stretched and unstretched papillary muscles. This study showed that myocardial stretch was a sufficient stimulus for the induction of TNF- α mRNA biosynthesis. The functional significance of the intramyocardial production of TNF-α was determined by examining cell motion in isolated contracting cardiac myocytes treated with superfusates from pressure- overloaded and control hearts. These studies showed that cell motion was depressed in myocytes treated with superfusates from the pressure-overloaded hearts but was normal with the superfusates from the control hearts. Finally, hemodynamic pressure overloading in vive under physiological conditions was also shown to result in de novo intramyocardial TNF-α mRNA biosynthesis. In conclusion, this study constitutes the initial demonstration that the adult mammalian myocardium elaborates biologically active TNF-α, both ex vive and in vivo, in response to hemodynamic pressure overloading.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalCirculation Research
Volume81
Issue number2
DOIs
StatePublished - Jan 1 1997

Keywords

  • Gene expression
  • Myocyte
  • Pressure overload
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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