IL-10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury

Bagchi, Ashim K.; Surendran, Arun; Malik, Akshi; Jassal, Davinder S.; Ravandi, Amir; Singal, Pawan K.

doi:10.1038/s41598-020-68995-z

Cited by 18 publications

(11 citation statements)

References 56 publications

(91 reference statements)

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“…The anti-inflammatory role of IL-10 was suggested to contribute to reduced levels of IL-6 and TNF-α. Furthermore, in ischemia-reperfusion injury animal models, IL-10 mitigated inflammation and cardiomyocyte death by attenuating oxidized phospholipids-mediated lipid metabolic responses [ 67 ]; these findings in corroboration with our study support the potential of IL-10 therapy for the treatment of inflammatory diseases and conditions including CVD.…”

Section: Discussionsupporting

confidence: 88%

Upregulated miR-18a-5p in Colony Forming Unit-Hill’s in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study

et al. 2022

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Colony forming unit-Hill’s (CFU-Hill’s) colonies are hematopoietic-derived cells that participate in neovasculogenesis and serve as a biomarker for vascular health. In animals, overexpression of miR-18a-5p was shown to be pro-atherogenic. We had shown that well-controlled type 1 diabetes mellitus (T1DM) is characterized by an inflammatory state, endothelial dysfunction, and reduced number of CFU-Hill’s, a model of subclinical cardiovascular disease (CVD). MERIT study explored the role of miR-18a-5p expression in CFU-Hill’s colonies in T1DM, and the cardioprotective effect of metformin in subclinical CVD. In T1DM, miR-18a-5p was significantly upregulated whereas metformin reduced it to HC levels. MiR-18a-5p was inversely correlated with CFU-Hill’s colonies, CD34+, CD34+CD133+ cells, and positively with IL-10, C-reactive protein, vascular endothelial growth factor-D (VEGF-D), and thrombomodulin. The receiver operating characteristic curve demonstrated, miR-18a-5p as a biomarker of T1DM, and upregulated miR-18a-5p defining subclinical CVD at HbA1c of 44.5 mmol/mol (pre-diabetes). Ingenuity pathway analysis documented miR-18a-5p inhibiting mRNA expression of insulin-like growth factor-1, estrogen receptor-1, hypoxia-inducible factor-1α cellular communication network factor-2, and protein inhibitor of activated STAT 3, whilst metformin upregulated these mRNAs via transforming growth factor beta-1 and VEGF. We confirmed the pro-atherogenic effect of miR-18a-5p in subclinical CVD and identified several target genes for future CVD therapies.

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Section: Discussionsupporting

confidence: 88%

Upregulated miR-18a-5p in Colony Forming Unit-Hill’s in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study

et al. 2022

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“…We have reported that TLR2 dominates over TLR4 regulation through NF-kB mediated pathway and activation of IRAK2/M [ 23 , 24 ]. Later, we have shown that increased OxPCs may have worsen the I/R injury via TLR2 upregulation controlled by LOX-1 [ 44 ]. We now assume that iNOS is a major downstream mediator of inflammation in cardiomyocytes and causes DIC.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Promotes iNOS/NO and Influences Inflammation in the Development of Doxorubicin-Induced Cardiomyopathy

Bagchi

Malik

Akolkar³

et al. 2021

Antioxidants

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Doxorubicin (Dox) is known to cause heart failure in some cancer patients. Despite extensive studies over the past half century, the subcellular basis of Dox-induced cardiomyopathy (DIC) is still elusive. Earlier, we suggested that Dox causes a delayed activation of unfolded protein response (UPR) which may promote mitochondrial Bax activity leading to cardiomyocyte death. As a follow up, using NO donor, S-Nitroso-N-acetyl-d,l-penicillamine (SNAP), and/or NOS inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), we now show that endoplasmic reticulum (ER) stress promotes inflammation through iNOS/NO-induced TLR2 activation. In vivo Dox treatment increased mitochondrial iNOS to promote ER stress as there was an increase in Bip (Grp78) response, proapoptotic CHOP (DDIT3) and ER-mediated Caspase 12 activation. Increased iNOS activity is associated with an increase in TLR2 and TNF-α receptor associated factor 2 (TRAF2). These two together with NF-κB p105/50 expression and a synergistic support through ER stress, promote inflammatory response in the myocardium leading to cell death and ultimately fostering DIC conditions. In the presence of NOS inhibitor, such detrimental effects of Dox were inhibited, suggesting iNOS/NO as key mediators of Dox-induced inflammatory as well as apoptotic responses.

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“…They observed that changes in CL, PC, phosphatidylinositol monomannoside, sphingomyelin, sulfatide, and ambiguous or unidentified lipids occur mainly after 48 h of I/R (I/R-48) and normalized or suppressed at I/R-72. ROS also increase the levels of oxidative phosphatidylcholines (OxPCs) in the I/R injury in the heart [ 46 ]. OxPCs may trigger apoptosis through phosphorylation of p38 mitogen-activated protein kinase (p38MAPK).…”

Section: Lipidomicsmentioning

confidence: 99%

“…There is ample evidence of adverse accumulation of FAs in renal I/R injury, which ultimately may give rise to lipotoxicity [ 27 , 46 ]. The term “lipotoxicity” refers to the condition with an unwanted accumulation of lipids in non-adipose tissues that are incapable of metabolizing them.…”

Section: Lipid Metabolism In I/r Injurymentioning

confidence: 99%

Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

Todorović

Đurašević

Stojković

et al. 2021

IJMS

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Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.

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IL-10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury

Cited by 18 publications

References 56 publications

Upregulated miR-18a-5p in Colony Forming Unit-Hill’s in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study

Upregulated miR-18a-5p in Colony Forming Unit-Hill’s in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study

Endoplasmic Reticulum Stress Promotes iNOS/NO and Influences Inflammation in the Development of Doxorubicin-Induced Cardiomyopathy

Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

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