Related Experiment Video
Updated: Jul 3, 2026
06:22
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Maturation-induces endothelial dysfunction via vascular inflammation in diabetic mice
Cuihua Zhang1, Yoonjung Park, Andrea Picchi
1Dept. of Internal Medicine, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, MO 65211, USA. zhangcu@missouri.edu
Basic Research in Cardiology
|July 5, 2008
Summary
Vascular inflammation and elevated TNFalpha contribute to endothelial dysfunction in type II diabetes. Blocking TNFalpha improved function, highlighting its role in disease progression.
Area of Science:
- Cardiovascular Biology
- Metabolic Diseases
- Inflammation Research
Background:
- Type II diabetes is associated with endothelial dysfunction.
- Maturation-induced vascular inflammation may contribute to this dysfunction.
- Tumor Necrosis Factor-alpha (TNFalpha) is a potential mediator of inflammation in diabetes.
Purpose of the Study:
- To investigate the role of maturation-induced vascular inflammation and TNFalpha in the development of endothelial dysfunction in type II diabetes.
- To determine the impact of TNFalpha inhibition on endothelial function in diabetic mice.
Main Methods:
- Utilized control (Db/db) and type II diabetic (db/db) mice at various ages (6, 12, 18, 24 weeks).
- Assessed vasodilation using sodium nitroprusside (SNP) and acetylcholine (ACh).
- Administered neutralizing antibodies to TNFalpha and inhibitors of superoxide production (apocynin, rotenone).
- Measured plasma TNFalpha, TNFalpha receptor 1 (TNFR1) expression, and superoxide production.
Main Results:
- Endothelial function, assessed by ACh-induced dilation, was impaired in db/db mice from 12 weeks onwards, worsening with age.
- SNP-induced dilation remained comparable between groups.
- TNFalpha antibody treatment ameliorated endothelial dysfunction in db/db mice, particularly in younger animals.
- Elevated TNFalpha and TNFR1 expression and increased superoxide production were observed in db/db mice even before diabetes onset (6 weeks), with progressive increases over time.
- NAD(P)H oxidase and mitochondrial respiratory chain were identified as sources of superoxide.
Conclusions:
- Maturation-induced vascular inflammation, mediated by TNFalpha, plays a critical role in endothelial dysfunction in type II diabetes.
- Elevated TNFalpha and TNFR1 expression contribute to superoxide production via NAD(P)H oxidase and mitochondria, leading to progressive endothelial dysfunction.
- Targeting TNFalpha may be a therapeutic strategy for preventing or treating endothelial dysfunction in type II diabetes.
Related Concept Videos
01:28Diabetic Nephropathy
Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...
01:27Diabetic Retinopathy
DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...
01:24Type II Diabetes II: Pathophysiology
PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
01:26Type I Diabetes II: Pathophysiology
Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...
01:22Diabetic Neuropathy
DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...
01:26Type II Diabetes I: Introduction
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...