Mitochondria-targeted esculetin mitigates atherosclerosis in the setting of aging via the modulation of SIRT1-mediated vascular cell senescence and mitochondrial function in Apoe mice

Karnewar, Santosh; Pulipaka, Sriravali; Katta, Sujana; Panuganti, Devayani; Neeli, Praveen Kumar; Thennati, Rajamannar; Jerald, Mahesh Kumar; Kotamraju, Srigiridhar

doi:10.1016/j.atherosclerosis.2022.07.012

Cited by 25 publications

(14 citation statements)

References 53 publications

(76 reference statements)

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“…Mitochondrial fusion/ disassembly and mitochondrial biogenesis also play important roles in maintaining the homeostasis of the mitochondrial internal environment. 36 The results of our study showed that the level of FIS1 was significantly increased, and the level of MFN1 was significantly decreased in senescent mMECs. Puerarin could reverse these changes.…”

Section: Discussionmentioning

confidence: 90%

Puerarin Delays Mammary Gland Aging by Regulating Gut Microbiota and Inhibiting the p38MAPK Signaling Pathway

Liu,

Hu,

Zhang

et al. 2024

J. Agric. Food Chem.

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Mammary gland aging is one of the most important problems faced by humans and animals. How to delay mammary gland aging is particularly important. Puerarin is a kind of isoflavone substance extracted from Pueraria lobata, which has antiinflammatory, antioxidant, and other pharmacological effects. However, the role of puerarin in delaying lipopolysaccharide (LPS)induced mammary gland aging and its underlying mechanism remains unclear. On the one hand, we found that puerarin could significantly downregulate the expression of senescence-associated secretory phenotype (SASP) and age-related indicators (SA-β-gal, p53, p21, p16) in mammary glands of mice. In addition, puerarin mainly inhibited the p38MAPK signaling pathway to repair mitochondrial damage and delay mammary gland aging. On the other hand, puerarin could also delay the cellular senescence of mice mammary epithelial cells (mMECs) by targeting gut microbiota and promoting the secretion of gut microbiota metabolites. In conclusion, puerarin could not only directly act on the mMECs but also regulate the gut microbiota, thus, playing a role in delaying the aging of the mammary gland. Based on the above findings, we have discovered a new pathway for puerarin to delay mammary gland aging.

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Section: Discussionmentioning

confidence: 90%

Puerarin Delays Mammary Gland Aging by Regulating Gut Microbiota and Inhibiting the p38MAPK Signaling Pathway

Liu,

Hu,

Zhang

et al. 2024

J. Agric. Food Chem.

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“…Recently, new mitochondria targeted-antioxidants, preferentially delivered to the mitochondrial compartment to scavenge mitochondria-derived ROS, have been proposed to increase antioxidant levels specifically in mitochondria [ 90 , 91 ]. In particular, Karnewar et al [ 92 ] have demonstrated that an an alkyl TPP + -tagged esculetin (mitochondria-targeted esculetin or Mito-Esc) reduces atherosclerosis by delaying vascular senescence and pro-inflammatory processes, and by increasing mitochondrial biogenesis. Furthermore, in humans, it has been demonstrated that pioglitazone, an anti-diabetic drug, stimulates mitochondrial biogenesis in the subcutaneous fat of patients with diabetes mellitus, a strong risk factor for atherosclerotic disease, contributing to the lipid-lowering effect of this drug [ 93 ].…”

Section: Clinical Perspectives and Therapeutic Implications: Somethin...mentioning

confidence: 99%

Mitochondrial Dysfunction: The Hidden Player in the Pathogenesis of Atherosclerosis?

Ciccarelli

Conte

Cimmino

et al. 2023

IJMS

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Atherosclerosis is a multifactorial inflammatory pathology that involves metabolic processes. Improvements in therapy have drastically reduced the prognosis of cardiovascular disease. Nevertheless, a significant residual risk is still relevant, and is related to unmet therapeutic targets. Endothelial dysfunction and lipid infiltration are the primary causes of atherosclerotic plaque progression. In this contest, mitochondrial dysfunction can affect arterial wall cells, in particular macrophages, smooth muscle cells, lymphocytes, and endothelial cells, causing an increase in reactive oxygen species (ROS), leading to oxidative stress, chronic inflammation, and intracellular lipid deposition. The detection and characterization of mitochondrial DNA (mtDNA) is crucial for assessing mitochondrial defects and should be considered the goal for new future therapeutic interventions. In this review, we will focus on a new idea, based on the analysis of data from many research groups, namely the link between mitochondrial impairment and endothelial dysfunction and, in particular, its effect on atherosclerosis and aging. Therefore, we discuss known and novel mitochondria-targeting therapies in the contest of atherosclerosis.

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“…Wang et al reported that administration of roscovitine, a CDK5 inhibitor, inhibited cellular senescence and prevented the development of atherosclerosis in the aortas of hypercholesterolemic ApoE −/− mice [25]. Kotamraju et al found that treatment with mitochondria‐targeted esculetin (Mito‐Esc) attenuated atherosclerosis progression by delaying vascular aging and pro‐inflammatory processes [103], and treatment with metformin significantly alleviated vascular senescence and inhibited age‐associated formation of atherosclerotic plaque in ApoE −/− mice [104]. In addition, inhibition of the NF‐κβ pathway also alleviated vascular senescence and AS [82], and deletion of the IFN‐γ or IFN‐γ‐receptor induced a more stable plaque phenotype and blocked the pathogenesis of AS [66].…”

Section: Targeting Senescence Of Vecs Induced By Pro‐inflammatory Cyt...mentioning

confidence: 99%

Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis

Shang

Liu

2023

Fundamemntal Clinical Pharma

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Atherosclerosis (AS) is a chronic inflammatory vascular disease, and aging is a major risk factor. The accumulation of senescent vascular endothelial cells (VECs) often leads to chronic inflammation and oxidative stress and induces endothelial dysfunction, contributing to the occurrence and development of AS. Senescent cells can secrete a variety of pro‐inflammatory cytokines to induce the senescence of adjacent cells in a paracrine manner, leading to the transmission of signaling of cellular senescence to neighboring cells and the accumulation of senescent cells. Recent studies have demonstrated that several pro‐inflammatory cytokines, including IL‐17, TNF‐α, and IFN‐γ, can induce the senescence of VECs. This review summarizes and focuses on the pro‐inflammatory cytokines that often induce the senescence of VECs and the molecular mechanisms of these pro‐inflammatory cytokines inducing senescence of VECs. Targeting the senescence of VECs induced by pro‐inflammatory cytokines may provide a potential and novel strategy for the prevention and treatment of AS.

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Mitochondria-targeted esculetin mitigates atherosclerosis in the setting of aging via the modulation of SIRT1-mediated vascular cell senescence and mitochondrial function in Apoe mice

Cited by 25 publications

References 53 publications

Puerarin Delays Mammary Gland Aging by Regulating Gut Microbiota and Inhibiting the p38MAPK Signaling Pathway

Puerarin Delays Mammary Gland Aging by Regulating Gut Microbiota and Inhibiting the p38MAPK Signaling Pathway

Mitochondrial Dysfunction: The Hidden Player in the Pathogenesis of Atherosclerosis?

Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis

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