Atherosclerosis and Non-Alcoholic Fatty Liver Disease

Balta, Şevket

doi:10.1177/00033197221091317

Cited by 7 publications

(4 citation statements)

References 113 publications

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“…Additionally, studies showed Genistein treats NAFLD by targeting Thromboxane A2. Our findings regarding its effect on the expression regulation of genes related to Apoptosis ( NOS3 ), Thrombogertesis inflammation atherosclerosis 74 ( ICAM1 56 ), and Mesangial matrix expansion ( FN1 ) may suggest new drug treatment mechanisms for NAFLD ( Fig. S3 C ).…”

Section: Discussionmentioning

confidence: 84%

Pharmaceutical Repurposing Strategies for Metabolic Disorders: Insights from Mendelian Randomization Studies

Zhang,

Hu,

Hou

et al. 2024

Preprint

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Metabolic disorders (MDs) are a group of medical conditions that impact the metabolism. These complex processes may have common characteristics among various diseases, thereby suggesting the potential of drug repurposing. Employing Mendelian Randomization (MR), we constructed a causal network between 2,478 targetable drug-gene expressions (eQTLs) and 30 broadly reported metabolic disorders. Our study identified 499 drug target genes significantly associated with 27 metabolic disorders (|MR coefficient| > 0.2). Pathway enrichment analysis of drug target genes indicates that regulation of response stimulus may serve as a common pathway across 14 diseases. Based on 53 commonly used clinical drugs for 18 diseases, we elucidated novel therapeutic mechanisms of some drugs, such as the potential of Valproic Acid to treat Schizophrenia by affecting key genes in Alcoholism, SLC29A1, and HDAC4. Furthermore, we identified potential for drug repurposing in four diseases, with Manic Episode and Type 1 Diabetes sharing four novel drugs: Cannabidiol, Doxorubicin, Genistein, and Propylthiouracil. Additionally, we predicted 189 potential therapeutic drugs affecting the causal genes of diseases. Overall, we established a causal network between metabolic disorders and drug target genes, explored possible pathways for drug action on disease treatment, and proposed drug repurposing strategies for four diseases.

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Section: Discussionmentioning

confidence: 84%

Pharmaceutical Repurposing Strategies for Metabolic Disorders: Insights from Mendelian Randomization Studies

Zhang,

Hu,

Hou

et al. 2024

Preprint

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“…The presence of a hypercoagulable state in patients with MASLD has the potential to result in the formation of microthrombi in the hepatic veins and arteries, leading to disrupted blood flow [58]. Increased rates of clinically significant thrombotic events, such as pulmonary embolism, deep vein thrombosis, and portal vein thrombosis, are explicable by abnormalities at all stages of hemostasis [83,84], including a condition of hypercoagulation derived from decreased levels of PAI-1 [61,72,73].…”

Section: Coagulation Dysfunctionsmentioning

confidence: 99%

“…The clinical presentations of atherosclerotic disease encompass coronary artery disease, peripheral arterial disease, and stroke. Atherosclerosis (AS) is a dynamic and progressive condition that results from the convergence of aberrant lipid metabolism, endothelial dysfunction, and inflammation [83,84,105,193]. An essential stage in the inflammatory process involves the penetration of monocytes into the subendothelial region of major arteries and their subsequent transformation into tissue macrophages.…”

Section: Adiponectinmentioning

confidence: 99%

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Pezzino,

Luca,

Castorina

et al. 2024

Life

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The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.

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“…The underlying mechanisms that link MAFLD to an increased risk of CVD primarily involve heightened inflammation, insulin resistance, oxidative stress, and perturbations in hepatic metabolites ( 8 , 9 ). Specifically, MAFLD has garnered substantial attention for its role in promoting systemic inflammation through hepatic steatosis-secreted inflammatory proteins such as interleukin-6, C-reactive protein, fibrinogen, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha ( 10 ). These inflammatory proteins augment the uptake of plasma-derived lipoproteins by macrophages, forming foam cells laden with lipids and initiating the development of atherosclerotic lesions by activating the adaptive immune system ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis

Wang,

Guo,

Qiu

et al. 2024

Front. Endocrinol.

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BackgroundLimited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM).MethodThis study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS.ResultsThe prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31–3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%.ConclusionSII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

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Atherosclerosis and Non-Alcoholic Fatty Liver Disease

Cited by 7 publications

References 113 publications

Pharmaceutical Repurposing Strategies for Metabolic Disorders: Insights from Mendelian Randomization Studies

Pharmaceutical Repurposing Strategies for Metabolic Disorders: Insights from Mendelian Randomization Studies

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis

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