Endothelial dysfunction caused by circulating microparticles from diabetic mice is reduced by PD98059 through ERK and ICAM-1

Taguchi, Kumiko; Kaneko, Nozomu; Okudaira, Kanami; Matsumoto, Takayuki; Kobayashi, Tsuneo

doi:10.1016/j.ejphar.2021.174630

Cited by 5 publications

(13 citation statements)

References 37 publications

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“…Therefore, we focused on the effects of ESAX on vascular function in DM. Our observation of an impaired ACh-induced endothelium-dependent vascular relaxation response in DM mice is consistent with previous reports 14,15 . Moreover, we found that ACh-induced endothelialdependent vascular NO production and relaxation response were improved by ESAX administration in DM mice.…”

Section: Effects Of Esax and Icam-1 On The No Production In Aortassupporting

confidence: 94%

“…Since ERK1/2-containing DM-derived MPs attached strongly to the aortas and induced eNOS-containing MP release from the endothelial cells of the aortas 14,15 , the role of the MP attachment factor in the ERK1/2-containing DM-derived MPs-induced expression of ERK1/2, eNOS, and intercellular adhesion molecule-1 (ICAM-1), an attachment factor, was evaluated. The higher expression of ERK1/2 and ICAM-1 was observed in the control aortas in response to DM-derived MPs (Fig.…”

Section: Effect Of Esax On Erk1/2 Enos and Icam-1 In Mpstreated Aortasmentioning

confidence: 99%

“…A number of studies have revealed that circulating MPs in pathological conditions can lead to the dysfunction or impairment of vascular endothelial cells 9,11,12 . Our previous work demonstrated that the amount of platelet-derived MPs increases in DM and that the rising MP levels impair vascular endothelialdependent relaxation by releasing endothelium-derived MPs containing eNOS [13][14][15] . Thus, MPs are considered markers of endothelial dysfunction in DM.…”

Section: Introductionmentioning

confidence: 99%

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Effect of esaxerenone on circulating microparticles and vascular endothelial function in diabetic mice

Taguchi,

Kondo,

Matsumoto

et al. 2024

Preprint

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Endothelial dysfunction exacerbates hypertension and other vascular complications in diabetes mellitus (DM). Circulating microparticles (MPs) and extracellular vesicles released in patients with DM have emerged as novel regulators of endothelial dysfunction. The obstruction of mineralocorticoid receptors (MRs) is a potential therapeutic approach to reduce cardiovascular complications. Their impact on the obstruction of MRs on circulating MPs and endothelial dysfunction in DM remains unclear. DM was induced in mice through a single intravenous dose of streptozotocin (STZ; 200 mg/kg). Esaxerenone (ESAX; 3 mg/kg/day), a MR blocker was administered via diet for 8 weeks. In this study, the aortas of the DM group showed the endothelial dysfunction and the administration of ESAX ameliorated the endothelial-dependent responses. Moreover, ESAX influences the impaired endothelial-dependent responses of DM-derived MPs. Interestingly, MP levels increased in DM whereas decreased after ESAX administration. In the aorta, the DM-derived MPs increased the expression of intercellular adhesion molecule-1 (ICAM-1). ESAX inhibited the adhesion of DM-derived MPs. Moreover, the ICAM-1 inhibitor A205804 shows similar effects as ESAX. These results indicate that the release and adhesion properties of MPs can be partially obstructed by ESAX via the ICAM-1 signaling pathway, which clarifies the other functions beyond the anti-hypertensive effects of ESAX.

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Section: Effects Of Esax and Icam-1 On The No Production In Aortassupporting

confidence: 94%

Section: Effect Of Esax On Erk1/2 Enos and Icam-1 In Mpstreated Aortasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of esaxerenone on circulating microparticles and vascular endothelial function in diabetic mice

Taguchi,

Kondo,

Matsumoto

et al. 2024

Preprint

Self Cite

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“…Likewise, excessive erythrocytosis exhibited by Andean highlanders also induce ED by means of dysfunctional circulating EVs [ 65 ]. Extracellular signal-regulated kinase (ERK) 1 embedded in platelet EVs from a mouse model of diabetes induce ED via intracellular adhesion molecule 1 (ICAM-1) [ 66 ]. Senescent EC-derived MVs (eMVs) from ACS patients induce premature ED and thrombogenicity through the angiotensin II–induced NADPH oxidase system [ 67 ].…”

Section: Evs As Pathophysiological Drivers Of Atherothrombosismentioning

confidence: 99%

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Suades

Greco

Padró

et al. 2022

Cells

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Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis.

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“…PD98059 is a potent and selective ERK inhibitor that specifically inhibits MAPK kinase activation in both in vivo and in vitro experiments [24,25]. In order to judge if the activating effect of CYP on IEC-6 cells is via the MAPK signaling pathway, the PD98059 inhibitor was added to DMEM medium and configured as a 10 µM solution.…”

Section: Inhibition Of Mapks Using Specific Inhibitorsmentioning

confidence: 99%

The Molecular Mechanism of Yam Polysaccharide Protected H2O2-Induced Oxidative Damage in IEC-6 Cells

Shen

Cai

et al. 2023

Foods

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Oxidative stress is involved in maintaining homeostasis of the body, and an in-depth study of its mechanism of action is beneficial for the prevention of chronic illnesses. This study aimed to investigate the protective mechanism of yam polysaccharide (CYP) against H2O2-induced oxidative damage by an RNA-seq technique. The expression of genes and the function of the genome in the process of oxidative damage by H2O2 in IEC-6 cells were explored through transcriptomic analysis. The results illustrated that H2O2 damaged cells by promoting cell differentiation and affecting tight junction proteins, and CYP could achieve cell protection via restraining the activation of the MAPK signaling pathway. RNA-seq analysis revealed that H2O2 may damage cells by promoting the IL-17 signaling pathway and the MAPK signaling pathway and so forth. The Western blot showed that the pretreatment of CYP could restrain the activation of the MAPK signaling pathway. In summary, this study demonstrates that the efficacy of CYP in modulating the MAPK signaling pathway against excessive oxidative stress, with a corresponding preventive role against injury to the intestinal barrier. It provides a new perspective for the understanding of the preventive role of CYP on intestinal damage. These findings suggest that CYP could be used as oxidation protectant and may have potential application prospects in the food and pharmaceutical industries.

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Endothelial dysfunction caused by circulating microparticles from diabetic mice is reduced by PD98059 through ERK and ICAM-1

Cited by 5 publications

References 37 publications

Effect of esaxerenone on circulating microparticles and vascular endothelial function in diabetic mice

Effect of esaxerenone on circulating microparticles and vascular endothelial function in diabetic mice

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

The Molecular Mechanism of Yam Polysaccharide Protected H2O2-Induced Oxidative Damage in IEC-6 Cells

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