Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders

Antioxidants, Journal Year: 2022, Volume and Issue: 11(3), P. 555 - 555

Published: March 15, 2022

The heme oxygenase (HO) enzyme system catabolizes to carbon monoxide (CO), ferrous iron, and biliverdin-IXα (BV), which is reduced bilirubin-IXα (BR) by biliverdin reductase (BVR). HO activity represented two distinct isozymes, the inducible form, HO-1, a constitutive HO-2, encoded genes (HMOX1, HMOX2, respectively). HO-1 responds transcriptional activation in response wide variety of chemical physical stimuli, including its natural substrate heme, oxidants, phytochemical antioxidants. expression regulated NF-E2-related factor-2 counter-regulated Bach-1, heme-sensitive manner. Additionally, HMOX1 promoter polymorphisms have been associated with human disease. induction can confer protection inflammatory conditions through removal pro-oxidant potential catalyst lipid peroxidation, whereas iron released from may trigger ferritin synthesis or ferroptosis. production heme-derived reaction products (i.e., BV, BR) contribute HO-dependent cytoprotection via antioxidant immunomodulatory effects. BVR BR newly recognized roles regulation. CO alter mitochondrial function leading modulation downstream signaling pathways that culminate anti-apoptotic, anti-inflammatory, anti-proliferative This review will present evidence for beneficial effects diseases, cardiovascular disease (CVD), metabolic conditions, diabetes obesity, as well acute chronic diseases liver, kidney, lung. Strategies targeting pathway, genetic expression, application BR, gas, donor compounds show therapeutic organ ischemia/reperfusion injury. Evidence studies indicate represent biomarker oxidative stress various clinical while increases serum levels correlated inversely risk CVD Ongoing trials investigate

Language: Английский

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Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11629 - 11629

Published: Oct. 27, 2021

Obesity is now a worldwide epidemic ensuing an increase in comorbidities' prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes death world. Several studies provide evidence for association between MAFLD atherosclerosis cardio-metabolic disorders, including CVDs coronary heart stroke. Therefore, combination MAFLD/NASH associated with vascular risk progression, but underlying mechanisms linking are still under investigation. may probably be involved, hepatic/systemic atherogenic dyslipidemia, well pro-atherogenic, pro-coagulant, pro-inflammatory mediators released from steatotic/inflamed liver. strongly which involved its pathogenesis progression to NASH. Insulin resistance major factor subjects without diabetes. However, T2D has been considered most common link CVD. This review summarizes obesity MAFLD, NASH, CVD, considering pathophysiological molecular these diseases. We also discuss NASH development structural functional cardiac alterations, pharmacological strategies treat prevention.

Language: Английский

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Metabolic dysfunction-associated fatty liver disease and implications for cardiovascular risk and disease prevention

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Dec. 3, 2022

The newly proposed term "metabolic dysfunction-associated fatty liver disease" (MAFLD) is replacing the old "non-alcoholic (NAFLD) in many global regions, because it better reflects pathophysiology and cardiometabolic implications of this common disease. change terminology from NAFLD to MAFLD not simply a single-letter an acronym, since defined by set specific positive diagnostic criteria. In particular, definition specifically incorporates within classification recognized cardiovascular risk factors. Although convincing evidence supports significant association between both MAFLD, with increased CVD morbidity mortality, neither nor have received sufficient attention Cardiology community. fact, there paucity scientific guidelines focusing on burdensome disease professional societies. This Perspective article discusses rationale clinical relevance for Cardiologists definition.

Language: Английский

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Cardiovascular Complications of Diabetes: From Microvascular to Macrovascular Pathways

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 24, 2023

Diabetes mellitus, with a growing risk of developing complications, has significant negative impact on cardiovascular health, including microvascular and macrovascular issues. This thorough narrative study methodically examines the complex connection between problems diabetes. We start by thoroughly introducing diabetes classifying its various forms, discussing global impact. Then, we examine retinopathy, nephropathy, neuropathy in detail, illuminating their biology, clinical presentations, treatment options. Moving to consequences, investigate relationships coronary artery disease, stroke, peripheral arterial emphasizing factors, diagnostic standards, plans designed for people The review analyzes pathophysiological pathways that link problems, endothelial dysfunction, chronic inflammation, immune system dysregulation, oxidative stress brought hyperglycemia. Additionally, critical function monitoring, assessment, predictive tools early detection. While highlighting current research paths need tailored medical approaches address this health issue, story also includes prevention management strategies, ranging from lifestyle changes medications. concludes providing summary information, gaps, advocating interdisciplinary efforts reduce effects

Language: Английский

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The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 22(10), P. 1999 - 2010.e8

Published: March 21, 2024

Language: Английский

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Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study

BMJ, Journal Year: 2024, Volume and Issue: unknown, P. e076388 - e076388

Published: Feb. 13, 2024

Abstract Objective To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular and all cause death in patients with type 2 diabetes mellitus (T2DM). Design Nationwide population based study. Setting Longitudinal cohort study Korea. Participants 7 796 763 participants National Health Screening Programme 2009 were divided into three groups on NAFLD status: no (fatty index<30); grade 1 (30≤fatty index<60); index≥60). Median follow-up was 8.13 years. Main outcome measures The primary incident (myocardial infarction, ischaemic stroke) or death. Results Of participants, 6.49% (n=505 763) had T2DM. More T2DM (34.06%) (26.73%) than those without (grade NAFLD: 21.20%; 10.02%). incidence rate (per 1000 person years) increased order NAFLD, rates higher five year absolute (no T2DM: 1.03, 95% confidence interval 1.02 to 1.04, 1.25, 1.24 1.26, respectively; 1.23, 1.22 1.50, 1.48 1.51, 1.42, 1.40 1.45, 2.09, 2.06 2.12, 3.34, 3.27 3.41, 3.68, 3.61 3.74, 3.94, 3.87 4.02, 4.25, 4.18 4.33, 4.66, 4.54 4.78, 5.91, 5.78 6.05, respectively). Patients a NAFLD. Risk differences between Conclusions seems be associated death, even mild group

Language: Английский

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Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2338 - 2338

Published: Feb. 16, 2024

Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90–95% of cases are type 2 diabetes mellitus. This partly attributed the surge prevalence obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as primary cause morbidity and mortality, placing substantial burden on healthcare systems due potential for macrovascular microvascular complications. this context, leptin, an adipocyte-derived hormone, plays fundamental role. hormone essential regulating cellular metabolism energy balance, controlling inflammatory responses, maintaining CV system homeostasis. Thus, leptin resistance not only contributes weight gain but may also lead increased cardiac inflammation, greater fibrosis, hypertension, impairment metabolism. Understanding relationship between obese individuals with DM (T2DM) could improve management prevention complication. Therefore, narrative review, we will discuss evidence linking presence, severity, and/or prognosis obesity T2DM regarding disease, aiming shed light implications better preventive strategies.

Language: Английский

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Nonalcoholic fatty liver disease (NAFLD) and associated mortality in individuals with type 2 diabetes, pre-diabetes, metabolically unhealthy, and metabolically healthy individuals in the United States

Metabolism, Journal Year: 2023, Volume and Issue: 146, P. 155642 - 155642

Published: June 26, 2023

Language: Английский

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Identification of biomarkers for the diagnosis of type 2 diabetes mellitus with metabolic associated fatty liver disease by bioinformatics analysis and experimental validation

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 28, 2025

Background Type 2 diabetes (T2DM) combined with fatty liver is a subtype of metabolic disease (MAFLD), and the relationship between T2DM MAFLD close mutually influential. However, connection mechanisms two are still unclear. Therefore, we aimed to identify potential biomarkers for diagnosing both conditions. Methods We performed differential expression analysis weighted gene correlation network (WGCNA) on publicly available data diseases in Gene Expression Omnibus database find genes related utilised protein–protein interactions (PPIs), Ontology, Kyoto Encyclopedia Genes Genomes T2DM-associated mechanisms. Candidate were screened using machine learning algorithms 12 cytoHubba algorithms, diagnostic model T2DM-related was constructed evaluated.The CIBERSORT method used investigate immune cell infiltration immunological significance central genes. Finally, collected whole blood from patients MAFLD, healthy individuals, high-fat, high-glucose high-fat models verify hub Results Differential WGCNA identified 354 dataset. The T2DM-peripheral mononuclear cells/liver dataset 91 secreted proteins. PPI revealed important modules pathogenic which contained 49 nodes, suggesting their involvement interaction, inflammation, other processes. TNFSF10, SERPINB2, TNFRSF1A only coexisting shared key proteins, enabling construction highly accurate disorders. Additionally, successfully produced. patterns SERPINB2 verified patient our cellular model. Immune dysregulation observed strongly linked regulation. Conclusion sensitivity accuracy predicting can be greatly improved TNFRSF1A. These may significantly influence development offering new options MAFLD.

Language: Английский

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PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4305 - 4305

Published: April 13, 2022

Peroxisome proliferator-activated receptors (PPAR), ligand-activated transcription factors of the nuclear hormone receptor superfamily, have been identified as key metabolic regulators in liver, skeletal muscle, and adipose tissue, among others. As a leading cause liver disease worldwide, non-alcoholic fatty (NAFLD) steatohepatitis (NASH) significant burden worldwide therapeutic strategies are needed. This review provides an overview evidence on PPAR-targeted treatment NAFLD NASH individuals with type 2 diabetes mellitus. We considered current from clinical trials observational studies well impact comorbid conditions such obesity, dyslipidemia, cardiovascular disease. Future areas research, possible sexually dimorphic effects therapies, briefly reviewed.

Language: Английский

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