The Mechanisms of the Development of Atherosclerosis in Prediabetes

Liang, Yin; Wang, Mengxue; Wang, Chen; Liu, Yun; Naruse, Keiji; Takahashi, Katsuroku

doi:10.3390/ijms22084108

Cited by 19 publications

(20 citation statements)

References 117 publications

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“…At the same time, hyperglycemia up-regulates chronic inflammatory markers, increases the production of reactive oxygen species (ROS), leads to metabolic disorders and promotes the occurrence of prediabetesrelated complications. 38 On the one hand, dietary intervention limited energy intake and alleviated metabolic stress faced by cells. On the other hand, some nutrients from a healthy diet have special protective effects on cells.…”

Section: Discussionmentioning

confidence: 99%

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes

Xu,

Li,

et al. 2024

Diabetes Metabolism Res

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ObjectivePrediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes‐related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors.MethodsThis prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow‐up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results.ResultsWe included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0‐1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5–6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5–6 versus 0‐1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively.ConclusionsCombined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.

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Section: Discussionmentioning

confidence: 99%

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes

Xu,

Li,

et al. 2024

Diabetes Metabolism Res

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“…Hyperglycemia leads to increased hematopoiesis and ROS-producing neutrophils, as well as to the production of extracellular vesicles from vascular endothelial cells and leukocytes, which, in turn, facilitate atherosclerosis via ROS-producing NADPH oxidase and LDL-scavenging CD36. They also carry specific miRNAs that promote hematopoiesis and inflammation [47].…”

Section: Classical Risk Factors Hypercholesterolemiamentioning

confidence: 99%

Therapeutic Strategies and Chemoprevention of Atherosclerosis: What Do We Know and Where Do We Go?

Aprotosoaie

Costache

2022

Pharmaceutics

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Despite progress in understanding the pathogenesis of atherosclerosis, the development of effective therapeutic strategies is a challenging task that requires more research to attain its full potential. This review discusses current pharmacotherapy in atherosclerosis and explores the potential of some important emerging therapies (antibody-based therapeutics, cytokine-targeting therapy, antisense oligonucleotides, photodynamic therapy and theranostics) in terms of clinical translation. A chemopreventive approach based on modern research of plant-derived products is also presented. Future perspectives on preventive and therapeutic management of atherosclerosis and the design of tailored treatments are outlined.

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“…As Figure 1A shows, CAR protein expression was detected by immunofluorescence analysis, and we observed that CAR was mainly localized in the cytoplasm compartment of endothelial cells (Figure 1A). We next studied the effect of CAR-selective agonist 6-(4-chlorophenyl) imidazo [2,1-b] [1,3]thiazole-5-carbaldehyde O- (3,4-dichlorobenzyl)oxime (CITCO) on endothelial cell viability. For this purpose, HUVEC monolayers were pretreated with CITCO (0.1-3 µM) or vehicle (0.1% DMSO) for 24 h. As illustrated in Figure 1B, no effects on endothelial cell viability were detected at the different CITCO concentrations used.…”

Section: Car Is Expressed In Human Endothelial Cellsmentioning

confidence: 99%

“…Atherosclerosis involves an inflammatory response, consisting of intimal accumulation of leukocytes and lipid-laden macrophages throughout the entire atherogenic process [1,2]. Endothelial dysfunction, one of the earliest stages of atherogenesis, leads to a prothrombotic and proinflammatory phenotype of the endothelium which induces leukocyte attachment and subsequent migration [3].…”

Section: Introductionmentioning

confidence: 99%

Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium

López-Riera

Ortega

Hueso

et al. 2021

IJMS

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Leukocyte cell recruitment into the vascular subendothelium constitutes an early event in the atherogenic process. As the effect of the constitutive androstane receptor (CAR) on leukocyte recruitment and endothelial dysfunction is poorly understood, this study investigated whether the role of CAR activation can affect this response and the underlying mechanisms involved. Under physiological flow conditions, TNFα-induced endothelial adhesion of human leukocyte cells was concentration-dependently inhibited by preincubation of human umbilical arterial endothelial cells with the selective human CAR ligand CITCO. CAR agonism also prevented TNFα induced VCAM-1 expression, as well as MCP-1/CCL-2 and RANTES/CCL-5 release in endothelial cells. Suppression of CAR expression with a small interfering RNA abrogated the inhibitory effects of CITCO on these responses. Furthermore, CITCO increased interaction of CAR with Retinoid X Receptor (RXR) and reduced TNFα-induced p38-MAPK/NF-κB activation. In vivo, using intravital microscopy in the mouse cremasteric microcirculation treatment with the selective mouse CAR ligand TCPOBOP inhibited TNFα-induced leukocyte rolling flux, adhesion, and emigration and decreased VCAM-1 in endothelium. These results reveal that CAR agonists can inhibit the initial inflammatory response that precedes the atherogenic process by targeting different steps in the leukocyte recruitment cascade. Therefore, CAR agonists may constitute a new therapeutic tool in controlling cardiovascular disease-associated inflammatory processes.

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The Mechanisms of the Development of Atherosclerosis in Prediabetes

Cited by 19 publications

References 117 publications

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes

Therapeutic Strategies and Chemoprevention of Atherosclerosis: What Do We Know and Where Do We Go?

Activation of the Constitutive Androstane Receptor Inhibits Leukocyte Adhesiveness to Dysfunctional Endothelium

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