Deficiency of liver-X-receptor-α reduces glucose uptake and worsens post-myocardial infarction remodeling

Ji, Qingqi; Zhao, Yichao; Yuan, Ancai; Pu, Jun; He, Ben

doi:10.1016/j.bbrc.2017.05.072

Cited by 8 publications

(4 citation statements)

References 38 publications

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“…It has been reported that the reduced glucose uptake at the level of the heart cells due to the genetically induced liver X receptor α (LXRα) deficiency leads to a severe damage after MI, which indirectly confirms that during ischaemia the adaptive transfer mechanism of the energy production is activated in the heart, from the fatty acid metabolism to the glucose metabolism which has greater oxidative utilization for synthesis of Adinosine Tri Phosphate (ATP). 10 A healthy heart quickly activates this cardio protective mechanism in the condition of ischaemia which reduces the damage. 11 This is delayed or absent in a weaker state of the person.…”

Section: Introductionmentioning

confidence: 99%

Improvements in long standing cardiac pathologies by individualized homeopathic remedies: A case series

Tenzera¹,

Djindjić

Mihajlovic-Elez³

et al. 2018

SAGE Open Medical Case Reports

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We present three cases of cardiac arrest at different stages of pathology. Acute myocardial infarction and resulting heart failure is emerging as the leading cause of mortality. In the long run, acute episodes and cardiac remodelling can cause considerable damage and result in heart failure. In these cases, individualized homeopathic therapy was instituted along with the conventional medicines and the results were encouraging. The changes in the laboratory diagnostic parameters (single-photon emission computed tomography, electrocardiograph, echocardiography and ejection fraction as the case may be) are demonstrated over time. The key result seen in all three cases was the preservation of general well-being while the haemodynamic states also improved. While the three cases provide evidence of positive outcomes for homeopathic therapy, more extensive studies are required in a hospital setting to establish the real extent to which this therapy may be employed.

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Section: Introductionmentioning

confidence: 99%

Improvements in long standing cardiac pathologies by individualized homeopathic remedies: A case series

Tenzera¹,

Djindjić

Mihajlovic-Elez³

et al. 2018

SAGE Open Medical Case Reports

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“…Moreover, although our study indicates a critical role of the novel LXRα-UHRF1-miR-26b signaling axis in AAA, we cannot rule out the possibility that other pathways controlled by LXR contribute to the observed phenotypes. Earlier work from our laboratory revealed that LXRα exerts beneficial effects on vulnerable atherosclerotic plaques and myocardial infarction 39,40 ; our current study depicts its deleterious effects in AAA. There are 2 possible explanations for this observation.…”

Section: Discussionmentioning

confidence: 50%

“…Earlier work from our laboratory revealed that LXRα exerts beneficial effects on vulnerable atherosclerotic plaques and myocardial infarction 39 , 40 ; our current study depicts its deleterious effects in AAA. There are 2 possible explanations for this observation.…”

Section: Discussionmentioning

confidence: 50%

LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p

Guo,

Zhong,

Zhao

et al. 2024

Circulation

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BACKGROUND: Abdominal aortic aneurysm (AAA) is a severe aortic disease without effective pharmacological approaches. The nuclear hormone receptor LXRα (liver X receptor α), encoded by the NR1H3 gene, serves as a critical transcriptional mediator linked to several vascular pathologies, but its role in AAA remains elusive. METHODS: Through integrated analyses of human and murine AAA gene expression microarray data sets, we identified NR1H3 as a candidate gene regulating AAA formation. To investigate the role of LXRα in AAA formation, we used global Nr1h3 -knockout and vascular smooth muscle cell–specific Nr1h3 -knockout mice in 2 AAA mouse models induced with angiotensin II (1000 ng·kg·min; 28 days) or calcium chloride (CaCl 2 ; 0.5 mol/L; 42 days). RESULTS: Upregulated LXRα was observed in the aortas of patients with AAA and in angiotensin II– or CaCl 2 -treated mice. Global or vascular smooth muscle cell–specific Nr1h3 knockout inhibited AAA formation in 2 mouse models. Loss of LXRα function prevented extracellular matrix degeneration, inflammation, and vascular smooth muscle cell phenotypic switching. Uhrf1 , an epigenetic master regulator, was identified as a direct target gene of LXRα by integrated analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing. Susceptibility to AAA development was consistently enhanced by UHRF1 (ubiquitin-like containing PHD and RING finger domains 1) in both angiotensin II– and CaCl 2 -induced mouse models. We then determined the CpG methylation status and promoter accessibility of UHRF1-mediated genes using CUT&Tag (cleavage under targets and tagmentation), RRBS (reduced representation bisulfite sequencing), and ATAC-seq (assay for transposase-accessible chromatin with sequencing) in vascular smooth muscle cells, which revealed that the recruitment of UHRF1 to the promoter of miR-26b led to DNA hypermethylation accompanied by relatively closed chromatin states, and caused downregulation of miR-26b expression in AAA. Regarding clinical significance, we found that underexpression of miR-26b-3p correlated with high risk in patients with AAA. Maintaining miR-26b-3p expression prevented AAA progression and alleviated the overall pathological process. CONCLUSIONS: Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA and provides potential biomarkers and therapeutic targets for AAA.

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“…Measurements of left parasternal long axes and M-mode images were acquired at a heart rate of 450-500 bpm. The left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were calculated as previously described [26]. Body temperature was maintained with the aid of a heating pad.…”

Section: Animals and The Establishment Of A Cardiac Arrest Andmentioning

confidence: 99%

Salvianolic Acid B Improves Postresuscitation Myocardial and Cerebral Outcomes in a Murine Model of Cardiac Arrest: Involvement of Nrf2 Signaling Pathway

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Survival and outcome of cardiac arrest (CA) are dismal despite improvements in cardiopulmonary resuscitation (CPR). Salvianolic acid B (Sal B), extracted from Salvia miltiorrhiza, has been investigated for its cardioprotective properties in cardiac remodeling and ischemic heart disease, but less is known about its role in CA. The aim of this study was to learn whether Sal B improves cardiac and neurologic outcomes after CA/CPR in mice. Female C57BL/6 mice were subjected to eight minutes of CA induced by an intravenous injection of potassium chloride (KCl), followed by CPR. After 30 seconds of CPR, mice were blindly randomized to receive either Sal B (20 mg/kg) or vehicle (normal saline) intravenously. Hemodynamic variables and indices of left ventricular function were determined before CA and within three hours after CPR, the early postresuscitation period. Sal B administration resulted in a remarkable decrease in the time required for the return of spontaneous circulation (ROSC) in animals that successfully resuscitated compared to the vehicle-treated mice. Myocardial performance, including cardiac output and left ventricular systolic (dp/dtmax) and diastolic (dp/dtmin) function, was clearly ameliorated within three hours of ROSC in the Sal B-treated mice. Moreover, Sal B inhibited CA/CPR-induced cardiomyocyte apoptosis and preserved mitochondrial morphology and function. Mechanistically, Sal B dramatically promoted Nrf2 nuclear translocation through the downregulation of Keap1, which resulted in the expression of antioxidant enzymes, including HO-1 and NQO1, thereby counteracted the oxidative damage in response to CA/CPR. The aforementioned antiapoptotic and antioxidant effects of Sal B were impaired in the setting of gene silencing of Nrf2 with siRNA in vitro model. These improvements were associated with better neurological function and increased survival rate (75% vs. 40%, p<0.05) up to 72 hours postresuscitation. Our findings suggest that the administration of Sal B improved cardiac function and neurological outcomes in a murine model of CA via activating the Nrf2 antioxidant signaling pathway, which may represent a novel therapeutic strategy for the treatment of CA.

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Deficiency of liver-X-receptor-α reduces glucose uptake and worsens post-myocardial infarction remodeling

Cited by 8 publications

References 38 publications

Improvements in long standing cardiac pathologies by individualized homeopathic remedies: A case series

Improvements in long standing cardiac pathologies by individualized homeopathic remedies: A case series

LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p

Salvianolic Acid B Improves Postresuscitation Myocardial and Cerebral Outcomes in a Murine Model of Cardiac Arrest: Involvement of Nrf2 Signaling Pathway

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