Plasma Nuclear and Mitochondrial DNA Levels, and Markers of Inflammation, Shock, and Organ Damage in Patients with Septic Shock

Timmermans, Kim; Kox, Matthijs; Scheffer, Gert Jan; Pickkers, Peter

doi:10.1097/shk.0000000000000549

Cited by 85 publications

(77 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cardiolipin, N -formylated peptides, oxidized mitochondrial DNA, and CpG islands, and mtHsp60 are all recognized as danger-associated molecular patterns (DAMPs). Cellular injury can result in the release of mitochondrial constituents, and a relationship between plasma mtDNA and inflammation has been demonstrated [103]. TLR9 recognizes mtDNA, and failure to properly degrade mtDNA by lysosomal endonucleases results in exacerbation of pressure overload and accelerated progression to dilated cardiomyopathy [95].…”

Section: Consequence Of Disrupted Mitochondrial Quality Controlmentioning

confidence: 99%

Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart

Gottlieb¹,

Thomas²

2017

Curr Pathobiol Rep

View full text Add to dashboard Cite

PURPOSE OF REVIEW Mitochondrial homeostasis and quality control are essential to maintenance of cardiac function and a disruption of this pathway can lead to deleterious cardiac consequences. RECENT FINDINGS Mitochondrial quality control has been described as a major homeostatic mechanism in cell. Recent studies highlighted that an impairment of mitochondrial quality control in different cell or mouse models is linked to cardiac dysfunction. Moreover, some conditions as aging, genetic mutations or obesity have been associated with mitochondrial quality control alteration leading to an accumulation of damaged mitochondria responsible for increased production of reactive oxygen species, metabolic inflexibility, and inflammation, all of which can have sustained effects on cardiac cell function and even cell death. SUMMARY In this review, we describe the major mechanisms of mitochondrial quality control, factors that can impair mitochondrial quality control, and the consequences of disrupted mitochondrial quality control.

show abstract

Section: Consequence Of Disrupted Mitochondrial Quality Controlmentioning

confidence: 99%

Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart

Gottlieb¹,

Thomas²

2017

Curr Pathobiol Rep

View full text Add to dashboard Cite

show abstract

“…The immune system and its interactions with extracellular mitochondrial components (mtDNA [70], formyl peptide [36], and Tfam [71]) thus play a crucial role in inducing both initial widespread inflammatory response (which contributes to mitochondrial dysfunction through oxidative stress) and later mitochondrial recovery and hormesis.…”

Section: Sepsis-induced Mitochondrial Dysfunction and Organ Failurementioning

confidence: 99%

Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

Maestraggi

Lebas

Clère-Jehl

et al. 2017

BioMed Research International

View full text Add to dashboard Cite

Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF) at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs). In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis”) translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

show abstract

“…of patients following trauma (25,26), in patients with myocardial (27,28) and neurologic tissue injury (29,30), and in setting of sepsis (31,32). However, the role of mitochondria-derived DAMPs (mtDAMPs) has not been investigated in the setting of brain death, nor has their effect on allograft function been described.…”

Section: Introductionmentioning

confidence: 99%