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Crit Care Med. 2017 Mar;45(3):407-414. doi: 10.1097/CCM.0000000000002207.

Widespread Down-Regulation of Cardiac Mitochondrial and Sarcomeric Genes in Patients With Sepsis.

Author information

1
1Center for Pharmacogenomics, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO. 2Center for Cardiovascular Research, Cardiovascular Division, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO. 3Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California, San Diego, CA. 4Department of Biomedical Engineering, George Washington University, Washington, DC. 5Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO.

Abstract

OBJECTIVES:

The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts.

DESIGN:

Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts.

SETTING:

ICUs at Barnes-Jewish Hospital, St. Louis, MO.

PATIENTS:

Twenty sepsis patients, 11 ischemic heart disease, nine dilated cardiomyopathy, and 11 nonfailing donors.

INTERVENTIONS:

None other than those performed as part of patient care.

MEASUREMENTS AND MAIN RESULTS:

Messenger RNA expression levels for 198 mitochondrially localized energy production components, including Krebs cycle and electron transport genes, decreased by 43% ± 5% (mean ± SD). Messenger RNAs for nine genes responsible for sarcomere contraction and excitation-contraction coupling decreased by 43% ± 4% in septic hearts. Surprisingly, the alterations in messenger RNA levels in septic cardiomyopathy were both distinct from and more profound than changes in messenger RNA levels in the hearts of patients with end-stage heart failure.

CONCLUSIONS:

The expression profile of messenger RNAs in the heart of septic patients reveals striking decreases in expression levels of messenger RNAs that encode proteins involved in cardiac energy production and cardiac contractility and is distinct from that observed in patients with heart failure. Although speculative, the global nature of the decreases in messenger RNA expression for genes involved in cardiac energy production and contractility suggests that these changes may represent a short-term adaptive response of the heart in response to acute change in cardiovascular homeostasis.

PMID:
28067713
PMCID:
PMC5315660
DOI:
10.1097/CCM.0000000000002207
[Indexed for MEDLINE]
Free PMC Article

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