Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3

Ye, Jingxue; Li, Lanfang; Wang, Min; Ma, Qiuxiao; Tian, Yu; Zhang, Qiong; Liu, Jiushi; Li, Bin; Zhang, Bengang; Liu, Haitao; Sun, Guibo

doi:10.3389/fimmu.2022.900254

Cited by 30 publications

(23 citation statements)

References 128 publications

(151 reference statements)

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“…Similarly, MCC950 significantly reduces plaque sizes in hyperlipidemic murine models, suggesting that NLRP3 inhibitors may be candidates for the treatment of atherosclerosis ( 143 ). The oral administration of MCC950 is a recently identified approach for reducing the severity of spontaneous chronic colitis in Winnie mice ( 144 ) and for suppressing human retinal endothelial cell dysfunction for the treatment of diabetic retinopathy induced by high glucose conditions ( 145 ). Furthermore, NLRP3 inflammasome activation in neurons mediates neuroinflammation in acute ischemic stroke, whereas MCC950 reduces CIRI by mitigating inflammation and preserving BBB integrity ( 146 ).…”

Section: Inhibitors Of the Nlrp3 Inflammasome Pathwaymentioning

confidence: 99%

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

et al. 2023

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The inflammasome regulates innate immunity by serving as a signaling platform. The Nod-like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor protein apoptosis-associated speck-like protein (ASC) and pro-caspase-1, is by far the most extensively studied and well-characterized inflammasome. A variety of stimuli can activate the NLRP3 inflammasome. When activated, the NLRP3 protein recruits the adaptor ASC protein and activates pro-caspase-1, resulting in inflammatory cytokine maturation and secretion, which is associated with inflammation and pyroptosis. However, the aberrant activation of the NLRP3 inflammasome has been linked to various inflammatory diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus and inflammatory bowel disease. Therefore, the NLRP3 inflammasome has emerged as a promising therapeutic target for inflammatory diseases. In the present review, systematic searches were performed using 'NLRP3 inhibitor(s)' and 'inflammatory disease(s)' as key words. By browsing the literature from 2012 to 2022, 100 articles were retrieved, of which 35 were excluded as they were reviews, editorials, retracted or unavailable online, and 65 articles were included. According to the retrieved literature, the current understanding of NLRP3 inflammasome pathway activation in inflammatory diseases was summarize, and inhibitors of the NLRP3 inflammasome pathway targeting the NLRP3 protein and other inflammasome components or products were highlighted. Additionally, the present review briefly discusses the current novel efforts in clinical research.

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Section: Inhibitors Of the Nlrp3 Inflammasome Pathwaymentioning

confidence: 99%

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

et al. 2023

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“…Diabetes is clinically associated with impaired endothelial function, worsened by severe hyperglycemia. 8 When plaques are damaged and rupture, prothrombotic molecules are exposed to the coagulation system to inhibit blood flow. 9 Statins are widely used in the treatment of atherosclerosis due to their excellent efficacy in reducing lowdensity lipoprotein levels.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Other risk factors include diabetes developing in the early stages of insulin-dependent and insulin-resistant patients. Diabetes is clinically associated with impaired endothelial function, worsened by severe hyperglycemia …”

Section: Introductionmentioning

confidence: 99%

Anti-Atherosclerosis and Anti-Hyperlipidemia Functions of Terminalia catappa Fruit

Tabansi,

Dahiru,

Patrick

et al. 2023

ACS Omega

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Background: Atherosclerosis is a chronic pathological condition that has remained clinically silent for decades, and the epidemic has continued to be on the rise due to risk factors, including diet, lifestyle, hyperlipidemia, pathogenic microorganisms, and aging. Using various synthetic drugs in treating atherosclerosis is associated with a high risk of myositis, angioedema, myoglobinuria, and acute renal failure. Various side effects of the available drugs have been reported; attempts are underway to explore natural sources with antiatherosclerotic activity. Aim and objective: Using a diet-induced atherosclerosis rat model, the current study tested the hypothesis of antiatherosclerotic and antihyperlipidemic roles of Terminalia catappa fruit extracts. Materials and Methods: Atherosclerosis in Wistar rats was induced using an atherogenic diet. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), creatine kinase (CK), and lactate dehydrogenase (LDH) were determined using analytical kits. Results: Quantitative phytochemical analysis of the extracts demonstrated that the plant had flavonoids, saponins, tannins, terpenoids, alkaloids, cardiac glycosides, sterols, phenols, and anthraquinones. Diet-induced atherogenic Wistar rats showed a significant (p < 0.05) increase in total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol compared to the healthy control group; however, the atherogenic lipid profile was reversed by the treatment of T. catappa fruit extracts. The biochemical experiments demonstrate that T. catappa fruit extracts have an antihyperlipidaemic effect, shown by a decreased coronary risk index and the atherogenic index, and an increased cardioprotective index, compared to disease control. Conclusion: The current study indicates that T. catappa fruit extracts may contain bioactive molecules to treat atherosclerosis.

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“…In 2021, there were about 573 million adults with diabetes worldwide, of whom about 90% had T2DM ( IDF, 2021 ). In the process of T2DM, pathological factors such as glucose and lipid metabolism disorders, inflammatory stimulation or oxidative stress impair vascular endothelial cells, causing vascular endothelial dysfunction and subintimal lipid accumulation, eventually atherosclerosis ( La Sala et al, 2019 ; Poznyak et al, 2020 ; Ye et al, 2022a ). The carotid arteries are the earliest involved blood vessels in the development of atherosclerosis ( Beckman et al, 2002 ), which initially manifests as thickening of carotid intima-media.…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of Chinese herbal medicine as an add-on therapy for type 2 diabetes mellitus patients with carotid atherosclerosis: An updated meta-analysis of 27 randomized controlled trials

et al. 2023

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Background: Type 2 diabetes mellitus (T2DM) is a clinical metabolic syndrome characterized by persistent hyperglycemia. Patients with T2DM are more likely to have carotid atherosclerosis (CAS), which can lead to dizziness, amaurosis or even stroke. Chinese herbal medicine (CHM) has shown possible efficacy and safety in treating T2DM patients with CAS. However, the existing evidence was not robust enough and the results were out of date.Objective: This meta-analysis aimed to summarize the current evidence and systematically evaluate the effects of CHM on carotid plaque, glucose and lipid metabolism and vascular endothelial parameters in T2DM patients with CAS, providing a reference for subsequent research and clinical practice.Methods: This study was registered in PROSPERO as CRD42022346274. Both Chinese and English databases were searched from their inceptions to 16 July 2022. All retrieved studies were screened according to inclusion and exclusion criteria. Randomized controlled trials (RCTs) using oral CHM to treat T2DM patients with CAS were included. The literature quality was assessed using the risk of bias assessment tool in the Cochrane Handbook. Data extraction was conducted on the selected studies. Review Manager 5.4 and Stata 16.0 were used for meta-analysis. Sources of heterogeneity were explored by meta-regression or subgroup analysis. Funnel plot and Egger’s test were used to assess publication bias and the evidence quality was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE).Results: 27 eligible studies, involving 2638 patients, were included in this study. Compared with western medicine (WM) alone, the addition of CHM was significantly better in improving carotid intima-media thickness (CIMT) [mean difference (MD) = -0.11mm, 95% confidence interval (CI): −0.15 to −0.07, p < 0.01], carotid plaque Crouse score [MD = −1.21, 95%CI: −1.35 to −1.07, p < 0.01], total cholesterol (TC) [MD = −0.34 mmol/L, 95%CI: −0.54 to −0.14, p < 0.01], triglyceride (TG) [MD = −0.26 mmol/L, 95%CI: −0.37 to −0.15, p < 0.01], low-density lipoprotein cholesterol (LDL-C) [MD = −0.36 mmol/L, 95%CI: −0.47 to −0.25, p < 0.01], high-density lipoprotein cholesterol (HDL-C) [MD = 0.22 mmol/L, 95%CI: 0.13 to 0.30, p < 0.01], glycated hemoglobin (HbA1c) [MD = −0.36%, 95%CI: −0.51 to −0.21, p < 0.01], fasting blood glucose (FBG) [MD = −0.33 mmol/L, 95%CI: −0.50 to −0.16, p < 0.01], 2-h postprandial glucose (2hPG) [MD = −0.52 mmol/L, 95%CI: −0.95 to −0.09, p < 0.01], homeostasis model assessment of insulin resistance (HOMA-IR) [standardized mean difference (SMD) = −0.88, 95%CI: −1.36 to −0.41, p < 0.01] and homeostasis model assessment of beta-cell function (HOMA-β) [MD = 0.80, 95%CI: 0.51 to 1.09, p < 0.01]. Due to the small number of included studies, it is unclear whether CHM has an improving effect on nitric oxide (NO), endothelin-1 (ET-1), peak systolic velocity (PSV) and resistance index (RI). No serious adverse events were observed.Conclusion: Based on this meta-analysis, we found that in the treatment of T2DM patients with CAS, combined with CHM may have more advantages than WM alone, which can further reduce CIMT and carotid plaque Crouse score, regulate glucose and lipid metabolism, improve insulin resistance and enhance islet β-cell function. Meanwhile, CHM is relatively safe. However, limited by the quality and heterogeneity of included studies, the efficacy and safety of CHM remain uncertain. More high-quality studies are still needed to provide more reliable evidence for the clinical application of CHM.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022346274

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Diabetes Mellitus Promotes the Development of Atherosclerosis: The Role of NLRP3

Cited by 30 publications

References 128 publications

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

Anti-Atherosclerosis and Anti-Hyperlipidemia Functions of Terminalia catappa Fruit

The efficacy and safety of Chinese herbal medicine as an add-on therapy for type 2 diabetes mellitus patients with carotid atherosclerosis: An updated meta-analysis of 27 randomized controlled trials

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