Load-dependent and -independent regulation of proinflammatory cytokine and cytokine receptor gene expression in the adult mammalian heart

Georg Baumgarten, Pascal Knuefermann, Dinesh Kalra, Feng Gao, George E. Taffet, Lloyd Michael, Perry J. Blackshear, Ester Carballo, Natarajan Sivasubramanian, Douglas L. Mann

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100 Scopus citations

Abstract

Background - Although previous studies have examined the effects of acute hemodynamic pressure overload on proinflammatory cytokine gene expression, the effects of sustained hemodynamic overloading have not been examined. Methods and Results - Sustained hemodynamic pressure overloading was produced in mice by transverse constriction of the aorta. Proinflammatory cytokine and cytokine receptor gene expression were determined by ribonuclease protection assays (RPA) at 6 hours and at 3, 7, 14 and 35 days after banding. M-mode echocardiography was used to assess left ventricular structure and function at identical time points. RPA showed that tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6 mRNA levels were maximal at 6 hours and returned to baseline levels within 72 hours. There was a significant increase in IL-1RII and IL-6Rα receptor mRNA levels after overloading but no significant increase in TNFR1, TNFR2, IL-1RI, or gp130 mRNA levels. The transient increase in expression of proinflammatory cytokine gene expression was not explained by changes in left ventricular loading conditions, left ventricular wall stress, desensitization of proinflammatory genes, or decreased nuclear factor-κB activation. It is interesting that transverse constriction of the aorta provoked an increase in the expression of tristetraprolin, a homeostatic zinc finger protein that is known to destabilize TNF mRNA. Conclusion - Sustained hemodynamic overloading provokes a transient increase in proinflammatory cytokine and cytokine receptor gene expression; however, the decrease in proinflammatory cytokine gene expression occurred in the absence of changes in loading conditions, suggesting that the expression of proinflammatory cytokines in the heart is regulated, at least in part, by load-dependent and load-independent mechanisms.

Original languageEnglish
Pages (from-to)2192-2197
Number of pages6
JournalCirculation
Volume105
Issue number18
DOIs
StatePublished - May 7 2002
Externally publishedYes

Keywords

  • Cytokines
  • Gene expression
  • Growth factors
  • Hypertrophy
  • Remodeling

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    Baumgarten, G., Knuefermann, P., Kalra, D., Gao, F., Taffet, G. E., Michael, L., Blackshear, P. J., Carballo, E., Sivasubramanian, N., & Mann, D. L. (2002). Load-dependent and -independent regulation of proinflammatory cytokine and cytokine receptor gene expression in the adult mammalian heart. Circulation, 105(18), 2192-2197. https://doi.org/10.1161/01.CIR.0000015608.37608.18