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Atherosclerosis I: Introduction01:30

Atherosclerosis I: Introduction

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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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Peripheral artery disease (PAD) predominantly results from atherosclerosis, which involves the accumulation of fatty deposits, or plaques, within the walls of arteries. This causes them to narrow and harden, significantly reducing blood flow. PAD predominantly affects the legs but also impacts other areas, such as the arms, thereby impairing overall circulation and organ function.Etiology of PAD:The principal cause of PAD is atherosclerosis, which results from fatty deposits inside the arterial...
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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...
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Nursing management for a patient with arteriosclerosis involves a comprehensive approach focusing on lifestyle modification, disease monitoring, education, and symptomatic care. Here is an overview of effective nursing strategies:Assessment and Monitoring: Initial and ongoing assessments are crucial. Nurses must document the patient's medical history, including any hypertension, diabetes, hyperlipidemia, and other cardiovascular diseases. Assessments also cover family history and lifestyle...
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Paraoxonase 1 and atherosclerosis.

Paul N Durrington1, Bilal Bashir1,2, Handrean Soran1,2

  • 1Cardiovascular Research Group, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.

Frontiers in Cardiovascular Medicine
|March 6, 2023
PubMed
Summary

Paraoxonase 1 (PON1) protects against oxidative damage and atherosclerotic cardiovascular disease (ASCVD), especially in diabetes. Low PON1 activity is linked to increased ASCVD risk, highlighting a need for PON1-boosting therapies.

Keywords:
PON1 polymorphismcardiovascular diseasehigh density lipoproteinlipid peroxidationparaoxonase 1paraoxonase 1 activity

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Area of Science:

  • Biochemistry
  • Cardiovascular Science
  • Molecular Biology

Background:

  • Paraoxonase 1 (PON1) is an HDL-associated enzyme with hydrolytic activity against organophosphates, lactones, and lipid hydroperoxides.
  • PON1 is crucial for HDL's protective role against LDL and cell membrane oxidative modification, dependent on its lipid environment.
  • Reduced PON1 activity is observed in dyslipidemia, diabetes, and inflammatory conditions, correlating with increased atherosclerotic cardiovascular disease (ASCVD) events.

Purpose of the Study:

  • To review the multifaceted roles of PON1 in protecting against oxidative stress and cardiovascular disease.
  • To discuss factors influencing PON1 activity, including its localization, genetic polymorphisms, and interactions with other proteins.
  • To highlight the therapeutic potential of modulating PON1 activity for managing ASCVD, particularly in high-risk populations.

Main Methods:

  • Review of existing literature on PON1's biochemical properties, physiological functions, and clinical relevance.
  • Analysis of studies investigating PON1 polymorphisms and their impact on enzyme activity and disease susceptibility.
  • Examination of experimental models (gene ablation/overexpression) and in vitro studies on PON1 structure-activity relationships.

Main Results:

  • PON1's antioxidant function is dependent on its association with HDL lipids, converting lipid peroxidation products to harmless carboxylic acids.
  • Serum PON1 activity is inversely associated with ASCVD incidence, particularly in diabetic and established ASCVD patients.
  • PON1 activity is modulated by genetic variations (e.g., Q192R polymorphism) and interactions with other lipoproteins and inflammatory markers.

Conclusions:

  • PON1 plays a vital protective role in preventing oxidative damage and reducing ASCVD risk.
  • Therapeutic strategies aimed at increasing PON1 activity are warranted, especially for individuals with diabetes and dyslipidemia.
  • Further research into specific PON1-raising medications is needed to effectively combat cardiovascular disease.