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Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood
Scott A Hagen1, Amy L Kondyra, Hilary P Grocott
1Pediatric Critical Care Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Insights
Cardiopulmonary bypass (CPB) significantly lowers G protein-coupled receptor kinases (GRKs) in immune cells due to increased interleukin-6 (IL-6). Recovery of these kinases after surgery is variable, suggesting a potential role in patient outcomes.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Molecular Biology
Background:
- Cardiopulmonary bypass (CPB) in cardiac surgery is linked to organ injury and a proinflammatory response, marked by increased plasma interleukin-6 (IL-6).
- Elevated IL-6 is observed in inflammatory conditions like rheumatoid arthritis, where it correlates with reduced G protein-coupled receptor kinases (GRKs).
- This study investigates if CPB-induced IL-6 increases lead to a decrease in GRKs within mononuclear cells, impacting inflammation regulation.
Purpose of the Study:
- To determine if elevated interleukin-6 (IL-6) levels following cardiopulmonary bypass (CPB) reduce G protein-coupled receptor kinase (GRK) levels in mononuclear cells.
- To assess the impact of CPB on GRK activity and expression in patients undergoing cardiac surgery.
Main Methods:
- Blood samples were collected from 15 patients before CPB, 2 hours after CPB, and on postoperative day one (POD1).
- Plasma IL-6 concentrations were measured using enzyme-linked immunosorbent assay (ELISA).
- GRK protein expression and activity were assessed via Western blot and rhodopsin phosphorylation assays.
Main Results:
- Plasma IL-6 levels increased over 20-fold post-CPB and remained elevated on POD1.
- Cytosolic GRK activity decreased by 39%, with significant reductions in GRK2 (90%) and GRK6 (65%).
- GRK activity and expression returned to baseline in many patients by POD1, but recovery was variable.
Conclusions:
- Cardiopulmonary bypass induces a substantial decrease in mononuclear cell GRKs.
- The recovery of GRK levels after CPB is inconsistent among patients.
- Further research is warranted to explore the clinical significance and potential of GRKs as outcome markers post-CPB.
Background:
Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation.
Methods:
Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively.
Results:
Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients.
Conclusions:
The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.
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