Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy

Salami, Oluwabukunmi Modupe; Habimana, Olive; Peng, Jin-Fu; Yi, Guanghui

doi:10.1007/s10557-022-07354-8

Cited by 7 publications

(5 citation statements)

References 170 publications

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“…In animal cardiomyocytes exposed to LPS, some immunosuppressants, such as cyclosporin A, generate inhibitory effects on mPTP opening 53–56 . In addition, verbascoside, which has been proved to exert antioxidative and neuroprotective effects, alleviates oxidative stress, inflammatory cell infiltration, and cardiomyocyte apoptosis in LPS‐induced SIC rat model 57 .…”

Section: Discussionmentioning

confidence: 99%

“…In animal cardiomyocytes exposed to LPS, some immunosuppressants, such as cyclosporin A, generate inhibitory effects on mPTP opening. 53 , 54 , 55 , 56 In addition, verbascoside, which has been proved to exert antioxidative and neuroprotective effects, alleviates oxidative stress, inflammatory cell infiltration, and cardiomyocyte apoptosis in LPS‐induced SIC rat model. 57 In our research, we found that Dioscin attenuated the role of LPS and had a protective effect on rat myocardial tissue, which provides a possibility for the development of drugs targeting immunity and inflammation in SIC diseases based on Dioscin.…”

Section: Discussionmentioning

confidence: 99%

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Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway

Zhang,

Zhi,

Liu

et al. 2024

Immunity Inflam & Disease

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BackgroundDioscin has many pharmacological effects; however, its role in sepsis‐induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model.MethodsThe SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4‐Hydroxy‐2‐nonenal (4‐HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B‐cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated‐p65 (p‐p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real‐time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and dihydroethidium staining assays.ResultsDioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4‐HNE level in SIC rats. Dioscin reversed LPS‐induced reduction on SOD, CAT, GSH, and Bcl‐2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p‐p65/p65 value in LPS‐induced H9c2 cells.ConclusionProtective effects of Dioscin against LPS‐induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway

Zhang,

Zhi,

Liu

et al. 2024

Immunity Inflam & Disease

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Section: Reviewmentioning

confidence: 99%

“…The treatment landscape for SCM carries significant implications, with current approaches predominantly focusing on supportive care, infection control, and hemodynamic support [ 5 , 45 - 46 ]. There is growing interest in therapeutic strategies targeting mitochondrial dysfunction in sepsis as a potential avenue for intervention [ 45 ]. Management typically entails the administration of vasopressors such as noradrenaline, with vasopressin emerging as a potentially effective option for septic shock in some instances [ 47 ].…”

Section: Reviewmentioning

confidence: 99%

Myocardial Injury as a Harbinger of Multi-organ Failure in Septic Shock: A Comprehensive Review

Singam

2024

Cureus

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Myocardial injury in the context of septic shock presents a multifaceted challenge in critical care medicine with implications for patient prognosis and therapeutic strategies. This comprehensive review explores the mechanisms, diagnostic approaches, and clinical implications of myocardial injury as a harbinger of multi-organ failure in septic shock. We delineate the pathophysiological processes underlying myocardial injury, including inflammation, oxidative stress, and microcirculatory dysfunction, and discuss the diagnostic utility of cardiac biomarkers and imaging modalities in identifying myocardial injury. Furthermore, we elucidate the prognostic significance of myocardial injury and its implications for patient management, highlighting the need for tailored therapeutic interventions to mitigate its adverse effects. Future research and clinical practice directions are also discussed, emphasizing the importance of personalized medicine approaches and multidisciplinary collaboration in optimizing outcomes for patients with septic shock-associated myocardial injury. This review aims to provide a comprehensive understanding of myocardial injury in septic shock and inform strategies for improving patient care in this challenging clinical scenario.

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“…Mitochondria, the cellular powerhouses, play a crucial role in cardiac energy metabolism and are increasingly recognized as central players in the pathogenesis of SIC [3,4]. Mitochondria, quintessential to cellular metabolism and energy production, are increasingly recognized as pivotal in the pathogenesis of sepsis-induced cardiomyopathy (SIC) [5,6]. In this condition, systemic inflammatory response to infection precipitates profound myocardial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

The DNA-dependent protein kinase catalytic subunit promotes sepsis-induced cardiac dysfunction through disrupting INF-2-dependent mitochondrial dynamics

Ma,

Zhou,

Zhang

et al. 2024

Int. J. Med. Sci.

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Sepsis-induced cardiomyopathy (SIC) represents a severe complication of systemic infection, characterized by significant cardiac dysfunction. This study examines the role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Inverted Formin 2 (INF2) in the pathogenesis of SIC, focusing on their impact on mitochondrial homeostasis and dynamics. Our research demonstrates that silencing DNA-PKcs alleviates lipopolysaccharide (LPS)-induced cardiomyocyte death and dysfunction. Using HL-1 cardiomyocytes treated with LPS, we observed that DNA-PKcs knockdown notably reverses LPS-induced cytotoxicity, indicating a protective role against cellular damage. This effect is further substantiated by the reduction in caspase-3 and caspase-9 activation, key markers of apoptosis, upon DNA-PKcs knockdown. Besides, our data further reveal that DNA-PKcs knockdown attenuates LPS-induced mitochondrial dysfunction, evidenced by improved ATP production, enhanced activities of mitochondrial respiratory complexes, and preserved mitochondrial membrane potential. Moreover, DNA-PKcs deletion counteracts LPS-induced shifts towards mitochondrial fission, indicating its regulatory influence on mitochondrial dynamics. Conclusively, our research elucidates the intricate interplay between DNA-PKcs and INF2 in the modulation of mitochondrial function and dynamics during sepsis-induced cardiomyopathy. These findings offer new insights into the molecular mechanisms underpinning SIC and suggest potential therapeutic targets for mitigating mitochondrial dysfunction in this critical condition.

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Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy

Cited by 7 publications

References 170 publications

Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway

Protective effects of Dioscin against sepsis‐induced cardiomyopathy via regulation of toll‐like receptor 4/MyD88/p65 signal pathway

Myocardial Injury as a Harbinger of Multi-organ Failure in Septic Shock: A Comprehensive Review

The DNA-dependent protein kinase catalytic subunit promotes sepsis-induced cardiac dysfunction through disrupting INF-2-dependent mitochondrial dynamics

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