The protective effect of high mobility group protein HMGA2 in pressure overload-induced cardiac remodeling

Wu, Qin; Yang, Xiao; Liu, Chen; Duan, Mingxia; Cai, Zhulan; Xie, Saiyang; Yuan, Yuan; Wu, Hongyan; Deng, Wei; Tang, Qi‐Zhu

doi:10.1016/j.yjmcc.2019.01.027

Cited by 25 publications

(14 citation statements)

References 27 publications

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“…Ulteriorly, Polvani et al [ 46 ] summarized that PPAR γ can activate Nrf-2 directly or indirectly via an upstream route. Based on the theory, Wu et al [ 47 ] discovered that overexpression of high mobility group protein AT-hook 2 (HMGA2) ameliorates cardiac remodeling in response to pressure overload via the activation of the PPAR γ /Nrf2 signaling pathway. Therefore, we speculated that the antipathological cardiac remodeling effect of NOB after MI was through activating PPAR γ and PGC1 α ; the potential downstream effectors of PPAR γ in the protective process could be Nrf-2/HO-1.…”

Section: Discussionmentioning

confidence: 99%

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

et al. 2021

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Rationale. Pathological cardiac remodeling serves as a vital mechanism during the progression from myocardial infarction (MI) to chronic heart failure (CHF). Nobiletin (NOB), an active monomer extracted from the peel of citrus fruit, has been reported to have beneficial effects in cardiovascular diseases. Our study was aimed at describing the specific mechanisms through which NOB protects against pathological cardiac remodeling after MI. Materials and Methods. C57BL/6 mice were treated with coronary artery ligation to generate an MI model, followed by treatment for 3 weeks with NOB (50 mg/kg/d) or vehicle (50 mg/kg/d), with or without the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d). Cardiac function (echocardiography, survival rate, Evans blue, and triphenyl tetrazolium chloride staining), fibrosis (Masson’s trichrome staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB)), hypertrophy (haematoxylin-eosin staining, wheat germ agglutinin staining, and qRT-PCR), and apoptosis (WB and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining) were evaluated. Hypoxia-induced apoptosis (TUNEL, WB) and phenylephrine- (PE-) induced pathological hypertrophy (immunofluorescence staining, qRT-PCR) models were established in primary neonatal rat ventricular myocytes (NRVMs). The effects of NOB with or without T0070907 were examined for the expression of PPARγ and PPARγ coactivator 1α (PGC1α) by WB in mice and NRVMs. The potential downstream effectors of PPARγ were further analyzed by WB in mice. Results. Following MI in mice, NOB intervention enhanced cardiac function across three predominant dimensions of pathological cardiac remodeling, which reflected in decreasing cardiac fibrosis, apoptosis, and hypertrophy decompensation. NOB intervention also alleviated apoptosis and hypertrophy in NRVMs. NOB intervention upregulated PPARγ and PGC1α in vivo and in vitro. Furthermore, the PPARγ inhibitor abolished the protective effects of NOB against pathological cardiac remodeling during the progression from MI to CHF. The potential downstream effectors of PPARγ were nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Conclusions. Our findings suggested that NOB alleviates pathological cardiac remodeling after MI via PPARγ and PGC1α upregulation.

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Section: Discussionmentioning

confidence: 99%

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

et al. 2021

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“…The luciferase activity was detected and analyzed with the Dual Luciferase Reporter Assay Kit (Promega) based on the manufacturer's instruction. 29…”

Section: Luciferase Assaymentioning

confidence: 99%

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

Wang

Jiang

et al. 2020

Clinical & Translational Med

174

125

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“…The mRNA expression of HMGA1, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) in heart tissue or cardiomyocytes were detected by Real-Time PCR (RT-PCR) according to our previous work [20]. Briefly, total RNA was extracted by TRIZOL (Invitrogen) and the quality of RNA extraction was evaluated by spectrophotometer A260/A280 and A230/A260 ratio.…”

Section: Western Blotting and Quantitative Real-time Pcrmentioning

confidence: 99%

The effect of HMGA1 in LPS-induced Myocardial Inflammation

et al. 2020

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Aims:The High Mobility Group A1 (HMGA1) proteins, serving as a dynamic regulator of gene transcription and chromatin remodeling, play an influential part in the pathological process of a large number of cardiovascular diseases. However, the precise role of HMGA1 in sepsis induced cardiomyopathy (SIC) remains unintelligible. This research was designed to illustrate the effect of HMGA1 involved in SIC. Methods and Results: Cardiomyocyte-specific HMGA1 overexpression was obtained using an adenoassociated virus system with intramyocardial injection in mice heart. The model of SIC in mice was constructed via intraperitoneal injection of lipopolysaccharide (LPS) for 6h. H9c2 rat cardiomyocytes was stimulated with LPS for 12h. HMGA1 expression was upregulated in murine inflammatory hearts as well as LPS stimulated H9c2 cardiomyocytes. HMGA1-overexpressing exhibited aggravated cardiac dysfunction, cardiac inflammation as well as cells apoptosis following LPS treatment both in vivo and in vitro experiment. Interestingly, HMGA1 knockdown in H9c2 cardiomyocytes attenuated LPS-induced cardiomyocyte inflammation, but aggravated cell apoptosis. Mechanistically, we found that overexpression of HMGA1 induced increased expression of cyclooxygenase-2 (COX-2). COX-2 inhibitor alleviated the aggravation of inflammation and apoptosis in HMGA1 overexpressed H9c2 cardiomyocytes whereas HMGA1 knockdown induced a reduction in signal transducer and activators of transcription 3 (STAT3) expression. STAT3 agonist reversed HMGA1 silence induced anti-inflammatory effects, while ameliorated cell apoptosis induced by LPS. Conclusion: In conclusion, our results suggest that overexpression of HMGA1 aggravated cardiomyocytes inflammation and apoptosis by up-regulating COX-2 expression, while silence of HMGA1 expression attenuated inflammation but aggregated cell apoptosis via down-regulation of STAT3.

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The protective effect of high mobility group protein HMGA2 in pressure overload-induced cardiac remodeling

Cited by 25 publications

References 27 publications

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

The effect of HMGA1 in LPS-induced Myocardial Inflammation

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