Widespread Down-Regulation of Cardiac Mitochondrial and Sarcomeric Genes in Patients With Sepsis
| Autor: | Douglas L. Mann, Ashwin Jain, Richard S. Hotchkiss, Igor R. Efimov, Sarah Evans, Belal Al Khiami, Bernard H. Brownstein, Justin M. Vader, Scot J. Matkovich |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Cardiomyopathy Dilated Male Sarcomeres medicine.medical_specialty Citric Acid Cycle Cardiomyopathy Myocardial Ischemia Down-Regulation 030204 cardiovascular system & hematology Critical Care and Intensive Care Medicine Mitochondria Heart Article Transcriptome Sepsis Contractility Electron Transport 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans RNA Messenger Aged Aged 80 and over Messenger RNA business.industry RNA Dilated cardiomyopathy Middle Aged medicine.disease 030104 developmental biology Endocrinology Heart failure Female business Cardiomyopathies |
| Zdroj: | Critical care medicine. 45(3) |
| ISSN: | 1530-0293 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|