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Related Concept Videos

Atherosclerosis I: Introduction01:30

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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...
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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...
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Atherosclerosis is a progressive disorder that leads to the thickening and narrowing of arterial walls due to plaque buildup. This condition can cause various symptoms depending on the arteries affected:Coronary Artery Disease (CAD): This condition affects the coronary arteries and may lead to chest pain (angina), shortness of breath (dyspnea), heart attacks, and other heart disease symptoms.Cerebrovascular Disease: This affects blood flow to the brain, causing transient ischemic attacks (TIAs)...
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Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
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Quantification of Atherosclerosis in Mice
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Accelerated atherosclerosis in beta-thalassemia.

Julian Hurtado1, Hassan Sellak1, Giji Joseph1

  • 1Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States.

American Journal of Physiology. Heart and Circulatory Physiology
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Beta-thalassemia (BT) accelerates atherosclerosis due to increased free heme from hemolysis. Hemopexin therapy reduced plaque buildup in BT mice and a hemolysis model, suggesting heme

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atherosclerosisbeta-thalassemia

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Area of Science:

  • Cardiovascular Biology
  • Hematology
  • Metabolic Diseases

Background:

  • Beta-thalassemia (BT) is associated with increased carotid intima-medial thickness, a marker of premature atherosclerosis.
  • The direct link between BT pathophysiology and atherosclerotic disease progression remains unclear.
  • Heme-mediated oxidative stress is hypothesized to promote atherosclerosis in BT due to hemolytic anemia and increased free heme.

Purpose of the Study:

  • To investigate the direct relationship between beta-thalassemia and atherosclerotic disease.
  • To evaluate the therapeutic potential of hemopexin (HPX) and deferiprone (DFP) in mitigating BT-associated atherosclerosis.

Main Methods:

  • Utilized wild-type (WT) and BT mice fed a high-fat diet with PCSK9 gain-of-function mutation.
  • Administered adeno-associated virus (AAV)-mediated hemopexin (HPX) therapy.
  • Assessed the impact of deferiprone (DFP)-mediated iron chelation.
  • Quantified atherosclerotic plaque burden via aortic en face and aortic root lesion analysis.

Main Results:

  • BT mice exhibited significantly elevated atherosclerotic plaque accumulation compared to WT controls.
  • HPX therapy reduced plaque area in both BT mice and a phenylhydrazine-induced hemolysis model.
  • DFP treatment decreased atherosclerosis in BT mice but offered no additive benefit when combined with HPX.

Conclusions:

  • Beta-thalassemia directly accelerates atherosclerosis, driven by intravascular hemolysis and increased free heme.
  • Hemopexin therapy effectively reduces atherosclerotic plaque burden in models of BT and hemolysis.
  • Iron chelation shows efficacy but does not enhance the benefits of hemopexin therapy in this context.