Glucose regulates the intrinsic inflammatory response of the heart to surgically induced hypothermic ischemic arrest and reperfusion

Ahmed S. Bux, Merry L. Lindsey, Hernan G. Vasquez, Heinrich Taegtmeyer, Romain Harmancey

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We investigated the isolated working rat heart as a model to study early transcriptional remodeling induced in the setting of open heart surgery and stress hyperglycemia. Hearts of male Sprague Dawley rats were coldarrested in Krebs-Henseleit buffer and subjected to 60 min normothermic reperfusion in the working mode with buffer supplemented with noncarbohydrate substrates plus glucose (25 mM) or mannitol (25 mM; osmotic control). Gene expression profiles were determined by microarray analysis and compared with those of nonperfused hearts. Perfused hearts displayed a transcriptional signature independent from the presence of glucose showing a more than twofold increase in expression of 71 genes connected to inflammation, cell proliferation, and apoptosis. These transcriptional alterations were very similar to the ones taking place in the hearts of open heart surgery patients. Prominent among those alterations was the upregulation of the three master regulators of metabolic reprogramming, MYC, NR4A1, and NR4A2. Targeted pathway analysis revealed an upregulation of metabolic processes associated with the proliferation and activation of macrophages and fibroblasts. Glucose potentiated the upregulation of a subset of genes associated with polarization of tissue reparative M2-like macrophages, an effect that was lost in perfused hearts from rats rendered insulin resistant by high-sucrose feeding. The results expose the heart as a significant source of proinflammatory mediators released in response to stress associated with cardiac surgery with cardiopulmonary bypass, and suggest a major role for glucose as a signal in the determination of resident cardiac macrophage polarization.

Original languageEnglish (US)
Pages (from-to)37-52
Number of pages16
JournalPhysiological genomics
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2017

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Reperfusion
Glucose
Thoracic Surgery
Up-Regulation
Macrophages
Macrophage Activation
Mannitol
Microarray Analysis
Cardiopulmonary Bypass
Transcriptome
Hyperglycemia
Sprague Dawley Rats
Sucrose
Buffers
Fibroblasts
Cell Proliferation
Insulin
Apoptosis
Inflammation
Gene Expression

Keywords

  • Cardiac surgery
  • Glucose
  • Inflammation
  • Insulin resistance
  • Macrophage polarization

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Glucose regulates the intrinsic inflammatory response of the heart to surgically induced hypothermic ischemic arrest and reperfusion. / Bux, Ahmed S.; Lindsey, Merry L.; Vasquez, Hernan G.; Taegtmeyer, Heinrich; Harmancey, Romain.

In: Physiological genomics, Vol. 49, No. 1, 01.01.2017, p. 37-52.

Research output: Contribution to journalArticle

Bux, Ahmed S. ; Lindsey, Merry L. ; Vasquez, Hernan G. ; Taegtmeyer, Heinrich ; Harmancey, Romain. / Glucose regulates the intrinsic inflammatory response of the heart to surgically induced hypothermic ischemic arrest and reperfusion. In: Physiological genomics. 2017 ; Vol. 49, No. 1. pp. 37-52.
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