Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Cardiopulmonary bypass (CPB) vs sham-operated controls

ABSTRACT: heart from rats exposed to cardiopulmonary bypass (CPB) vs sham-operated controls

ORGANISM(S): Rattus norvegicus

SUBMITTER: Mihai Podgoreanu

PROVIDER: E-GEOD-924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Differential cardiac gene expression during cardiopulmonary bypass: ischemia-independent upregulation of proinflammatory genes.

Podgoreanu Mihai V MV Michelotti Gregory A GA Sato Yukie Y Smith Michael P MP Lin Simon S Morris Richard W RW Grocott Hilary P HP Mathew Joseph P JP Schwinn Debra A DA

The Journal of thoracic and cardiovascular surgery 20050801 2

<h4>Objective</h4>Cardiac surgery with cardiopulmonary bypass induces both systemic and local inflammatory responses implicated in the pathogenesis of myocardial dysfunction. Multifactorial perioperative sources of myocardial injury complicate understanding of the molecular mechanisms involved. By using microarray technology, this study examines myocardial gene expression responses to cardiopulmonary bypass in the absence of cardioplegic arrest and ischemia-reperfusion injury.<h4>Methods</h4>We ...[more]

PMID: 16077395

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Project description:Cardiopulmonary bypass (CPB), the mechanical support required during the majority of cardiac surgeries, causes significant systemic inflammation and multi-organ dysfunction that is especially severe in neonatal patients. Currently, the limited understanding of the molecular mechanisms that underlie CPB-associated inflammation presents a significant barrier to the development of therapeutic interventions. To address this knowledge gap, we performed mRNA sequencing of total circulating leukocytes from neonatal patients undergoing CPB. The transcriptional signatures across 7 time points ranging from pre-CPB, during CPB, to 24 hours post-CPB were found to be dominated by myeloid cells, particularly monocytes. INTERLEUKIN-8 (IL8) and TUMOR NECROSIS FACTOR-α (TNFα) were two inflammatory cytokines specifically and robustly upregulated in the leukocytes from both CPB patients and piglets exposed to CPB. To delineate the mechanism how CPB activates cytokine production, we exposed THP-1 cells, a human monocyte cell line, in vitro to CPB-like conditions including artificial surfaces, high shear stress and cooling/rewarming. The in vitro CPB data recapitulated the in vivo CPB condition in that IL8 and TNFα were strongly upregulated. Shear stress was the major driver of cytokine expression as compared to the temperature or plastic exposure. Extracellular calcium influx was found essential for the shear-stress mediated upregulation of cytokines via the MEK/ERK/AP-1 and Calcineurin/NFAT pathways. After being exposed to CPB conditions, a subpopulation of THP-1 cells died by apoptosis and TNFα-mediated necroptosis, the latter form of which potentially contribute to the post-CPB tissue injuries. Together, our study is the first to elucidate the shear-stress modulated molecular mechanisms leading to systemic inflammation in pediatric CPB and the link between inflammation and organ damage. Calcium signaling pathways and TNFα signaling are novel targets for therapeutic development to improve clinical outcomes. To our knowledge, these are also the first data to implicate necroptosis in CPB and show that shear stress can activate necroptosis.

Dataset Information

Cardiopulmonary bypass (CPB) vs sham-operated controls

Publications

Differential cardiac gene expression during cardiopulmonary bypass: ischemia-independent upregulation of proinflammatory genes.

Similar Datasets

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