Purple sweet potato color inhibits endothelial premature senescence by blocking the NLRP3 inflammasome

Sun, Chunhui; Fan, Shao‐Hua; Wang, Xin; Lü, Jun; Zhang, Zifeng; Wu, Dongmei; Shan, Qun; Zheng, Yuxin

doi:10.1016/j.jnutbio.2015.04.012

Cited by 35 publications

(33 citation statements)

References 73 publications

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“…It has also been found that the mtROS-dependent activation of the endothelial NLRP3 inflammasome by hyperglycemia may be an important initiating mechanism for endothelial dysfunction, 13 and endothelial senescence could be mediated through mtROS and NLRP3 inflammasome signaling pathways. 41 Data from our current investigation complement those from previous studies on the role of mtROS and NLRP3 inflammasome in endothelial dysfunction, highlighting a potentially effective target for the prevention and treatment of endothelial dysfunction-related cardiovascular disease.…”

Section: Discussionsupporting

confidence: 76%

Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway

Chen

Zhu

Ran

et al. 2017

JAHA

400

276

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BackgroundTrimethylamine‐N‐oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation. However, the exact mechanism is currently unclear. Studies have established a central role of nucleotide‐binding oligomerization domain–like receptor family pyrin domain–containing 3 (NLRP3) inflammasome in the pathogenesis of vascular inflammation. Here, we examined the potential role of the NLRP3 inflammasome in TMAO‐induced vascular inflammation in vitro and in vivo and the underlying mechanisms.Methods and ResultsExperiments using liquid chromatography‐tandem mass spectrometry, Western blot, and fluorescent probes showed that TMAO‐induced inflammation in human umbilical vein endothelial cells (HUVECs) and aortas from ApoE−/− mice. Moreover, TMAO promoted NLRP3 and activated caspase‐1 p20 expression and caspase‐1 activity in vitro and in vivo. Notably, a caspase‐1 inhibitor (YVAD), an NLRP3 inhibitor (MCC950), as well as NLRP3 short interfering RNA attenuated TMAO‐induced activation of the NLRP3 inflammasome, subsequently leading to suppression of inflammation in HUVECs. TMAO additionally stimulated reactive oxygen species (ROS) generation, in particular, mitochondrial ROS, while inhibiting manganese superoxide dismutase 2 (SOD2) activation and sirtuin 3 (SIRT3) expression in HUVECs and aortas from ApoE−/− mice. TMAO‐induced endothelial NLRP3 inflammasome activation was ameliorated by the mitochondrial ROS scavenger Mito‐TEMPO, or SIRT3 overexpression in HUVECs. Conversely, TMAO failed to further inhibit magnesium SOD2 and activate the NLRP3 inflammasome or induce inflammation in SIRT3 short interfering RNA–treated HUVECs and aortas from SIRT3−/− mice.Conclusions TMAO promoted vascular inflammation by activating the NLRP3 inflammasome, and the NLRP3 inflammasome activation in part was mediated through inhibition of the SIRT3‐SOD2–mitochondrial ROS signaling pathway.

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Section: Discussionsupporting

confidence: 76%

Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway

Chen

Zhu

Ran

et al. 2017

JAHA

400

276

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“…Recently, some pieces of literature have reported that some beneficial substances can reduce the senescence of ECs, at least in part, by inhibiting NLRP3 activation. Sun et al demonstrated that purple sweet potato color (PSPC), one type of flavonoid derived from purple sweet potato, ameliorates endothelium senescence by restraining ROS production and NLRP3 inflammasome activation, and then reduces atherosclerotic lesions in insulin-resistant mice 76 . Additionally, they further investigated the correlation between NLRP3 inflammasome and autophagy and the underlying mechanisms of EC senescence.…”

Section: Nlrp3 Inflammasome Activation In Endothelial Cells' Senescencementioning

confidence: 99%

NLRP3 inflammasome in endothelial dysfunction

et al. 2020

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Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.

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“…The main manifestations of this process include organ weight loss, cell atrophy, cytoplasmic pigmentation, reduced functional metabolism, weakened adaptive capacity and low disease resistance (37). Investigation on aging has become a research hotspot (38). POI represents a spectrum of disorders in the female reproductive system that leads to ovarian dysfunction (39).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 improves pathological damages by activating the p21‑p53‑STK pathway in ovary and Bax‑Bcl2 in the uterus in premature ovarian insufficiency mouse models

Wang

Cheng

et al. 2020

Mol Med Rep

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Purple sweet potato color inhibits endothelial premature senescence by blocking the NLRP3 inflammasome

Cited by 35 publications

References 73 publications

Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway

Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway

NLRP3 inflammasome in endothelial dysfunction

Ginsenoside Rg1 improves pathological damages by activating the p21‑p53‑STK pathway in ovary and Bax‑Bcl2 in the uterus in premature ovarian insufficiency mouse models

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Purple sweet potato color inhibits endothelial premature senescence by blocking the NLRP3 inflammasome

Cited by 35 publications

References 73 publications

Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway

Trimethylamine‐N‐Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3‐SOD2‐mtROS Signaling Pathway

NLRP3 inflammasome in endothelial dysfunction

Ginsenoside Rg1 improves pathological damages by activating the&nbsp;p21‑p53‑STK pathway in ovary and Bax‑Bcl2 in the uterus in premature ovarian insufficiency mouse models

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Ginsenoside Rg1 improves pathological damages by activating the p21‑p53‑STK pathway in ovary and Bax‑Bcl2 in the uterus in premature ovarian insufficiency mouse models