Related Experiment Video
Updated: Jun 9, 2026
11:56
A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
Published on: April 11, 2014
Ascorbic acid prevents increased endothelial permeability caused by oxidized low density lipoprotein
1Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, USA. james.may@vanderbilt.edu
Free Radical Research
|September 7, 2010
Summary
Mildly oxidized low-density lipoprotein (mLDL) increases vascular permeability. Ascorbic acid, an antioxidant, was found to prevent and reverse this mLDL-induced endothelial dysfunction, suggesting its therapeutic potential.
Area of Science:
- Biochemistry
- Cell Biology
- Vascular Biology
Background:
- Mildly oxidized low-density lipoprotein (mLDL) acutely increases vascular endothelial permeability.
- This increased permeability allows molecules to cross the endothelial barrier, potentially contributing to endothelial dysfunction.
- Ascorbic acid is known to tighten the endothelial barrier.
Purpose of the Study:
- To investigate whether ascorbic acid can prevent the increase in endothelial permeability induced by mLDL.
- To explore the mechanisms underlying mLDL-induced endothelial permeability changes.
Main Methods:
- EA.hy926 endothelial cells were treated with mLDL.
- Intracellular glutathione (GSH) levels and mLDL oxidation were measured.
- Endothelial permeability to inulin and ascorbate was assessed using cells cultured on semi-permeable filters.
- The effects of microtubule and microfilament inhibitors, and intracellular calcium chelation were examined.
- The impact of intracellular ascorbate and other cell-penetrant antioxidants was evaluated.
Main Results:
- mLDL treatment decreased intracellular GSH and promoted mLDL oxidation in endothelial cells.
- mLDL significantly increased endothelial permeability to inulin and ascorbate within 2 hours.
- The mLDL-induced permeability increase was inhibited by microtubule and microfilament inhibitors but not by calcium chelation.
- Intracellular ascorbate effectively prevented and reversed the mLDL-induced increase in endothelial permeability.
- Other cell-penetrant antioxidants mimicked the protective effect of ascorbate.
Conclusions:
- Endothelial cell ascorbate plays a significant role in mitigating endothelial dysfunction caused by mLDL.
- Ascorbic acid and other antioxidants may represent a therapeutic strategy against mLDL-induced vascular permeability changes.
Related Concept Videos
01:26Atherosclerosis III: Management
Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
01:26Coronary Artery Disease II: Pathophysiology
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
01:26Coronary Artery Disease IV: Preventive Measures
Effective preventive measures for coronary artery disease (CAD) focus on controlling modifiable risk factors, including cholesterol abnormalities and lifestyle changes.Cholesterol ManagementFirst, the Mediterranean diet and the American Heart Association advocate for maintaining low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL, with a more stringent recommendation of below 70 mg/dL for individuals at high risk. LDL cholesterol, often termed "bad cholesterol," can lead to the...
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...
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...