microRNA-135a-5p regulates NOD-like receptor family pyrin domain containing 3 inflammasome-mediated hypertensive cardiac inflammation and fibrosis via thioredoxin-interacting protein

Chen, Hao; Qiao, Huilian; Zhao, Qiang; Wei, Fuling

doi:10.1080/21655979.2021.2024956

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…The NLRP3 inflammasome became our focus since it can bind directly to TXNIP [28] . Blocking their interaction is able to alleviate hypertensive cardiac inflammation and fibrosis [37] . However, little is known about the role of TXNIP and NLRP3 in post-MI fibrosis.…”

Section: Discussionmentioning

confidence: 99%

TXNIP aggravates cardiac fibrosis and dysfunction after myocardial infarction in mice by enhancing the TGFB1/Smad3 pathway and promoting NLRP3 inflammasome activation

Zhang¹,

Wang²,

Wang³

et al. 2023

ABBS

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Myocardial infarction (MI) results in high mortality. The size of fibrotic scar tissue following MI is an independent predictor of MI outcomes. Thioredoxin-interacting protein (TXNIP) is involved in various fibrotic diseases. Its role in post-MI cardiac fibrosis, however, remains poorly understood. In the present study, we investigate the biological role of TXNIP in post-MI cardiac fibrosis and the underlying mechanism using mouse MI models of the wild-type (WT), Txnip -knockout ( Txnip -KO) type and Txnip -knock-in ( Txnip -KI) type. After MI, the animals present with significantly upregulated TXNIP levels, and their fibrotic areas are remarkably expanded with noticeably impaired cardiac function. These changes are further aggravated under Txnip -KI conditions but are ameliorated in Txnip -KO animals. MI also leads to increased protein levels of the fibrosis indices Collagen I, Collagen III, actin alpha 2 (ACTA2), and connective tissue growth factor (CTGF). The Txnip -KI group exhibits the highest levels of these proteins, while the lowest levels are observed in the Txnip -KO mice. Furthermore, Txnip -KI significantly upregulates the levels of transforming growth factor (TGF)B1, p-Smad3, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), Cleaved Caspase-1, and interleukin (IL)1B after MI, but these effects are markedly offset by Txnip -KO. In addition, after MI, the Smad7 level significantly decreases, particularly in the Txnip -KI mice. TXNIP may aggravate the progression of post-MI fibrosis and cardiac dysfunction by activating the NLRP3 inflammasome, followed by IL1B generation and then the enhancement of the TGFB1/Smad3 pathway. As such, TXNIP might serve as a novel potential therapeutic target for the treatment of post-MI cardiac fibrosis.

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Section: Discussionmentioning

confidence: 99%

TXNIP aggravates cardiac fibrosis and dysfunction after myocardial infarction in mice by enhancing the TGFB1/Smad3 pathway and promoting NLRP3 inflammasome activation

Zhang¹,

Wang²,

Wang³

et al. 2023

ABBS

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“…Overall, the results suggest that miRNA‐135a‐5p exerts a regulatory role in hypertensive cardiac inflammation and fibrosis by targeting TXNIP and inhibiting NLRP3 inflammasome‐mediated inflammatory in signal 1 pathway. This highlights the therapeutic potential of miRNA‐135a‐5p as a potential target for the management of cardiac complications associated with hypertension 109 …”

Section: Noncoding Rnas In Cardiomyopathiesmentioning

confidence: 93%

“…Chen et al 109 explored the role of miRNA‐135a‐5p in regulating the NLRP3 inflammasome and its associated cardiac inflammation and fibrosis in the context of hypertension. The study demonstrates that miRNA‐135a‐5p has a pivotal involvement in modulating hypertensive cardiac inflammation and fibrosis by targeting TXNIP, which is known to activate the NLRP3 inflammasome.…”

Section: Noncoding Rnas In Cardiomyopathiesmentioning

confidence: 99%

“…The findings suggest that these exosomes deliver miRNA-148a to target TXNIP and inhibit the TLR4/ NF-κB/NLRP3 inflammasome pathway (or priming phase), resulting in reduced oxidative stress, inflammation, and tissue damage in the circumstances of myocardial I/R injury 108. Chen et al109 explored the role of miRNA-135a-5p in regulating the NLRP3 inflammasome and its associated cardiac inflammation and fibrosis in the context of hypertension. The study demonstrates that miRNA-135a-5p has a pivotal involvement in modulating hypertensive cardiac inflammation and fibrosis by targeting TXNIP, which is known to activate the NLRP3 inflammasome.…”

mentioning

confidence: 99%

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Crosstalk of NLRP3 inflammasome and noncoding RNAs in cardiomyopathies

Jafari,

Shahabi Rabori,

Zolfi Gol

et al. 2023

Cell Biochemistry & Function

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Cardiovascular diseases (CVDs) identified as a serious public health problem. Although there is a lot of evidence that inflammatory processes play a significant role in the progression of CVDs, however, the precise mechanism is not fully understood. Nevertheless, recent studies have focused on inflammation and its related agents. Nucleotide oligomerization domain‐, leucine‐rich repeat‐, and pyrin domain‐containing protein 3 (NLRP3) is a type of pattern recognition receptor (PRR) that can recognize pathogen‐associated molecular patterns and trigger innate immune response. NLRP3 is a component of the NOD‐like receptor (NLR) family and have a pivotal role in detecting damage to cardiovascular tissue. It is suggested that activation of NLRP3 inflammasome leads to initiating and propagating the inflammatory response in cardiomyopathy. So, late investigations have highlighted the NLRP3 inflammasome activation in various forms of cardiomyopathy. On the other side, it was shown that noncoding RNAs (ncRNAs), particularly, microRNAs, lncRNAs, and circRNAs possess a regulatory function in the immune system's inflammatory response, implicating their involvement in various inflammatory disorders. In addition, their role in different cardiomyopathies was indicated in recent studies. This review article provides a summary of recent advancements focusing on the function of the NLRP3 inflammasome in common CVDs, especially cardiomyopathy, while also discussing the therapeutic potential of inhibiting the NLRP3 inflammasome regulated by ncRNAs.

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“…In recent years, increasing evidence has shown that hypertension affects heart function by changing gene expression. MicroRNAs (miRNAs), such as miR‐1929‐3p (Y. Wang et al, 2020), miR‐495 (T. Zhou et al, 2018), and miR‐135a‐5p (Chen, Qiao, et al, 2022), were involved in the alteration of cardiac functions. Overexpression of these miRNAs could attenuate NLRP3‐mediated hypertensive cardiac inflammation and fibrosis.…”

Section: Nlrp3 Inflammasome and Hypertensive Todmentioning

confidence: 99%

Targeting the NLRP3 inflammasome for the treatment of hypertensive target organ damage: Role of natural products and formulations

Liao,

Han,

Shen

et al. 2023

Phytotherapy Research

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Background and AimHypertension is a major global health problem that causes target organ damage (TOD) in the heart, brain, kidney, and blood vessels. The mechanisms of hypertensive TOD are not fully understood, and its treatment is challenging. This review provides an overview of the current knowledge on the role of Nod‐like receptor pyrin domain containing 3 (NLRP3) inflammasome in hypertensive TOD and the natural products and formulations that inhibit it.MethodsWe searched PubMed, Web of Science, Google Scholar, and CNKI for relevant articles using the keywords “hypertension,” “target organ damage,” “NLRP3 inflammasome,” “natural products,” and “formulations.” We reviewed the effects of the NLRP3 inflammasome on hypertensive TOD in different organs and discussed the natural products and formulations that modulate it.Key resultsIn hypertensive TOD, the NLRP3 inflammasome is activated by various stimuli such as oxidative stress and inflammation. Activation of NLRP3 inflammasome leads to the production of pro‐inflammatory cytokines that exacerbate tissue damage and dysfunction. Natural products and formulations, including curcumin, resveratrol, triptolide, and allicin, have shown protective effects against hypertensive TOD by inhibiting the NLRP3 inflammasome.Conclusions and ImplicationsThe NLRP3 inflammasome is a promising therapeutic target in hypertensive TOD. Natural products and formulations that inhibit the NLRP3 inflammasome may provide novel drug candidates or therapies for hypertensive TOD. Further studies are needed to elucidate the molecular mechanisms and optimize the dosages of these natural products and formulations and evaluate their clinical efficacy and safety.

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microRNA-135a-5p regulates NOD-like receptor family pyrin domain containing 3 inflammasome-mediated hypertensive cardiac inflammation and fibrosis via thioredoxin-interacting protein

Cited by 8 publications

References 58 publications

TXNIP aggravates cardiac fibrosis and dysfunction after myocardial infarction in mice by enhancing the TGFB1/Smad3 pathway and promoting NLRP3 inflammasome activation

TXNIP aggravates cardiac fibrosis and dysfunction after myocardial infarction in mice by enhancing the TGFB1/Smad3 pathway and promoting NLRP3 inflammasome activation

Crosstalk of NLRP3 inflammasome and noncoding RNAs in cardiomyopathies

Targeting the NLRP3 inflammasome for the treatment of hypertensive target organ damage: Role of natural products and formulations

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