Endothelial dysfunction in hyperglycemia as a trigger of atherosclerosis
Hironori Nakagami1, Yasufumi Kaneda, Toshio Ogihara
1Division of Clinical Gene Therapy, Osaka University Graduate School of Medical, 2-2 Yamada-oka, Suita 565-0871, Japan.
Current Diabetes Reviews
|January 29, 2008
Summary
Statins may protect against cardiovascular disease in type 2 diabetes by inhibiting oxidative stress and improving endothelial function. These drugs offer benefits beyond cholesterol reduction, crucial for diabetic patients.
Area of Science:
- Cardiovascular Disease
- Endocrinology
- Molecular Biology
Background:
- Type 2 diabetes significantly increases risks for coronary heart disease and stroke.
- Endothelial cell dysfunction, driven by hyperglycemia, is a key factor in diabetic cardiovascular complications.
- Oxidative stress and reactive oxygen species (ROS) play critical roles in the progression of atherosclerosis.
Purpose of the Study:
- To investigate the molecular mechanisms linking hyperglycemia, endothelial dysfunction, and cardiovascular disease in type 2 diabetes.
- To explore the potential of HMG-CoA reductase inhibitors (statins) in mitigating high glucose-induced endothelial damage.
- To understand the role of NADPH oxidase and oxidative stress in diabetic cardiovascular pathology.
Main Methods:
- Analysis of high D-glucose effects on human endothelial cells (EC), including apoptosis pathways (bax-caspase) and anti-apoptotic factors (HGF).
- Investigation of oxidative stress markers and the involvement of NADPH oxidase in hyperglycemia.
- Evaluation of statins' potential to inhibit NADPH oxidase activation and ROS production.
Main Results:
- High D-glucose induces apoptosis in human EC via the bax-caspase pathway.
- Hepatocyte growth factor (HGF) acts as an anti-apoptotic factor through the phosphatidylinositol 3-kinase/Akt pathway.
- NADPH oxidase is a major source of ROS in cardiovascular cells, activated by hyperglycemia via protein kinase C.
- Statins may inhibit high glucose-induced NADPH oxidase activation, reducing ROS production.
Conclusions:
- Statins may offer protective cardiovascular benefits in type 2 diabetes through pleiotropic effects, including antioxidant actions and improved endothelial function.
- Inhibition of NADPH oxidase and subsequent ROS reduction is a potential mechanism for statin efficacy in diabetic patients.
- Statins show promise in preventing vascular events in type 2 diabetes, independent of LDL-cholesterol levels.
Related Concept Videos
01:29Hyperglycemia
Hyperglycemia is an abnormally high blood glucose level. It is diagnosed by fasting glucose ≥126 mg/dL, 2-hour oral glucose tolerance test (or OGTT) ≥200 mg/dL, random glucose ≥200 mg/dL with symptoms, or HbA1c ≥6.5%. However, HbA1c results may be unreliable in certain conditions, such as anemia or hemoglobinopathies, and the diagnosis should be confirmed unless classic symptoms are present. Postprandial hyperglycemia is typically considered significant when glucose levels exceed 180 mg/dL two...
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...
01:30Atherosclerosis I: Introduction
Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
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.
01:20Pathophysiology of Diabetes
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...
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...