Plasma mitochondrial DNA levels were independently associated with lung injury in elderly hip fracture patients

Zhang, Jian zheng; Wang, Juan; Qu, Wen chun; Wang, Xiao Wei; Liu, Zhi; Ren, Ji xin; Liang, Han; Sun, Chuiguo

doi:10.1016/j.injury.2017.01.009

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…Hip fracture is a common type of bone fracture in the elderly and is associated with high rates of mortality and a high incidence of complications that mainly result from immune disorders (e.g., rapid inflammatory response) [1]. Lung infection is the most severe of these complications, and previous studies have demonstrated that a hip fracture may subsequently contribute to a potentially fatal lung infection [2, 3]. For instance, hip fracture can affect the release of mitochondrial DNA release and induce lung injury via the TLR9/NF-kappa B (NF- κ B) pathway [4].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-205-5p Targets HMGB1 to Suppress Inflammatory Responses during Lung Injury after Hip Fracture

Chen

Sun

2019

BioMed Research International

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Hip fracture is the most common type of injury in elderly people and is associated with a high incidence of complications and risk of mortality. In these patients, subsequent pulmonary infection can contribute to the development of an acute lung injury, a consequence of the systemic inflammatory response induced by hip fracture. Although the crucial role of microRNAs (miRNAs) in inflammatory responses has been established, the functions of miRNAs in the inflammatory responses associated with lung injury after hip fracture remain poorly understood. In this study, we explored the potential role of miR-205-5p in lung injury after hip fracture in an in vivo hip fracture model and in vitro cultures of human pulmonary alveolar epithelial cells (HPAEpiC). An analysis of clinical serum samples revealed increased levels of miR-205-5p and high mobility group box 1 (HMGB1) after hip fracture. A bioinformatics analysis and dual-luciferase reporter assay identified HMGB1 as a potential target of miR-205-5p. The overexpression of miR-205-5p clearly reduced the expression of HMGB1 and inhibited NF-κB signaling, apoptosis, and proinflammatory cytokine production while enabling continued cell proliferation. Our results demonstrate that the upregulation of miR-205-5p suppresses inflammatory responses and promotes cell viability and proliferation by selectively targeting HMGB1 in the context of lung injury after hip fracture. Therefore, miR-205-5p may be an alternative target of therapeutic strategies for lung injury after hip fracture.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-205-5p Targets HMGB1 to Suppress Inflammatory Responses during Lung Injury after Hip Fracture

Chen

Sun

2019

BioMed Research International

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“…More and more researches have shown that elderly hip fracture induced systemic inflammatory response and ALI, which increased the incidence of pulmonary infection complications and mortality in the elderly patients [ 2 , 5 , 6 , 33 , 34 ]. Although many measures have been taken to deal with it, such as perioperative respiratory assessment and management, surgical technique amendment, and internal fixation instrument improvement, pulmonary infection rates still remain high in clinic; it is still the main cause of death in the elderly fracture patients [ 35 – 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Among these complications, lung infection is the most serious and fatal [ 3 ]. Recently, more and more researches have indicated that pulmonary infection after elderly hip fracture is related to ALI, which resulted from the systemic inflammatory responses induced by the trauma of hip fracture [ 4 – 6 ]. The older the patients are, the higher the risk of pulmonary complications is; it leads to higher mortality [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Serum miR-146a and miR-150 as Potential New Biomarkers for Hip Fracture-Induced Acute Lung Injury

Gan

Sun

Li³

et al. 2018

Mediators of Inflammation

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Background Acute lung injury (ALI) and subsequent pulmonary infection are the most severe and usually fatal complications for elderly hip fracture patients. It is necessary to find some biomarkers for early diagnosis and prognosis of it. Objective This study is aimed at examining the differential expression of miR-146a, miR-150, and cytokines (IL-6 and IL-10) between younger and elderly rats suffering from hip fracture and investigating the possible meaning of them in early diagnosis and prognosis of ALI after hip fracture. Methods and Subjects Elderly rats and younger rats were randomly divided into sham group and fracture group, respectively. Two fracture groups received hip fracture operations. The damage degree of ALI was evaluated by histological observation and pathological score. Cytokines were measured by ELISA; miR-146a and miR-150 were analysed by qRT-PCR. Results After treatment, compared with the corresponding sham groups, the pulmonary histological score, the serum miR-146a concentrations, and the cytokine (IL-6 and IL-10) levels in serum and BALF were significantly higher (the miR-150 were lower) in the fracture groups (with the exception of IL-6 of the younger fracture group at 72 h, all P < 0.05). Meanwhile, compared with the younger fracture group, the aforementioned variables were significantly higher (the miR-150 levels were lower) in the elderly fracture group (with the exception of serum IL-10 and pulmonary histological score at 8 h, all P < 0.05). The results of linear regression analysis showed that serum miR-146a and miR-150 were significantly associated with pulmonary histological score. Conclusion Hip fracture can result in significant systemic inflammation and ALI in the rats. Compared to the younger rats, the elderly rats suffered a more remarkable ALI after hip fracture. It may be related to the abnormal expression of miR-146a and miR-150. Serum miR-146a and miR-150 are potential biomarkers for diagnosis and prognosis of ALI after hip fracture.

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“…13,14 In both populations, plasma mtDNA is elevated and associated with mortality, [15][16][17][18][19] but clinical data linking mtDNA to ARDS are limited to one study in elderly patients with hip fractures and an unadjusted association of plasma mtDNA and ARDS in a mixed ICU population. 18,20 Clarifying the role of circulating mtDNA in major populations at risk for ARDS is of particular clinical relevance, as it could predict response to mtDNAtargeted therapies. Inhibitors of a major mtDNA receptor, Toll-like receptor 9, are already in clinical trials for use in autoimmune disorders, 21 and systemic administration of DNAse and Toll-like receptor 9 small interfering RNA reduced sepsis-induced organ dysfunction in preclinical and pilot human studies.…”

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confidence: 99%

Plasma Mitochondrial DNA Levels Are Associated With ARDS in Trauma and Sepsis Patients

Faust

Reilly

Anderson

et al. 2020

Chest

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BACKGROUND: Critically ill patients who develop ARDS have substantial associated morbidity and mortality. Circulating mitochondrial DNA (mtDNA) released during critical illness causes endothelial dysfunction and lung injury in experimental models. This study hypothesized that elevated plasma mtDNA is associated with ARDS in critically ill patients with trauma and sepsis.METHODS: Plasma mtDNA concentrations were measured at ED presentation and approximately 48 h later in separate prospective cohorts of critically ill patients with trauma and sepsis. ARDS was classified according to the Berlin definition. The association of mtDNA with ARDS was tested by using multivariable logistic regression, adjusted for covariates previously shown to contribute to ARDS risk in each population.RESULTS: ARDS developed in 41 of 224 (18%) trauma patients and in 45 of 120 (38%) patients with sepsis. Forty-eight-hour mtDNA levels were significantly associated with ARDS (trauma: OR, 1.58/log copies/mL; 95% CI, 1.14-2.19 [P ¼ .006]; sepsis: OR, 1.52/log copies/ mL; 95% CI, 1.12-2.06 [P ¼ .007]). Plasma mtDNA on presentation was not significantly associated with ARDS in either cohort. In patients with sepsis, 48-h mtDNA was more strongly associated with ARDS among those with a nonpulmonary infectious source (OR, 2.20/log copies/mL; 95% CI, 1.36-3.55 [P ¼ .001], n ¼ 69) than those with a pulmonary source (OR, 1.04/log copies/mL; 95% CI, 0.68-1.59 [P ¼ .84], n ¼ 51; P ¼ .014 for interaction).CONCLUSIONS: Plasma mtDNA levels were associated with incident ARDS in two critical illness populations. Given supportive preclinical data, our findings suggest a potential link between circulating mtDNA and lung injury and merit further investigation as a potentially targetable mediator of ARDS. CHEST 2020; 157(1):67-76

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Plasma mitochondrial DNA levels were independently associated with lung injury in elderly hip fracture patients

Cited by 18 publications

References 28 publications

MicroRNA-205-5p Targets HMGB1 to Suppress Inflammatory Responses during Lung Injury after Hip Fracture

MicroRNA-205-5p Targets HMGB1 to Suppress Inflammatory Responses during Lung Injury after Hip Fracture

Serum miR-146a and miR-150 as Potential New Biomarkers for Hip Fracture-Induced Acute Lung Injury

Plasma Mitochondrial DNA Levels Are Associated With ARDS in Trauma and Sepsis Patients

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