Damaged artery with oxidized lipids causing inflammation.

Unstable Plaques: How Oxidized Lipids Trigger Artery Trouble

"Discover how common substances found in artery plaques, 27-hydroxycholesterol and 4-hydroxynonenal, worsen the condition and what you can do."


Atherosclerosis is more than just clogged arteries; it's a complex inflammatory process that can lead to serious heart problems. One of the key factors involved in the progression of this disease is the activity of an enzyme system known as cyclooxygenase 2/membrane-bound prostaglandin E synthase 1 (COX-2/mPGES-1). When this system is overactive, it contributes to the instability of plaques, increasing the risk of rupture.

A major cause of this overactivity is the presence of oxidized lipids – harmful fats that accumulate when low-density lipoproteins (LDLs, or "bad" cholesterol) become damaged. Two specific oxidized lipids, 27-hydroxycholesterol (27-OH) and 4-hydroxynonenal (HNE), are found in high concentrations within atherosclerotic plaques. Researchers are working to understand exactly how these lipids contribute to plaque progression and instability.

New research sheds light on how 27-OH and HNE promote the up-regulation of COX-2 and mPGES-1. This, in turn, leads to increased production of a hormone-like substance called prostaglandin E2 (PGE2), as well as increased nitric oxide. This study will explore how those factors contribute to inflammation and matrix metalloproteinase production by activated macrophages which may cause eventual rupture of plaque contributing to matrix metalloproteinase production.

How 27-OH and HNE Fuel Artery Inflammation

Damaged artery with oxidized lipids causing inflammation.

The study focused on how 27-OH and HNE impact key inflammatory processes within cells. Researchers discovered that both 27-OH and HNE cause an increase in the production of COX-2 and mPGES-1 enzymes. This is a critical step because these enzymes work together to produce prostaglandin E2 (PGE2), a molecule known to promote inflammation.

To conduct the research, the scientists conducted tests on human promonocytic U937 cells to observe if 27-OH and HNE might enhance the production of certain pro-inflammatory cytokines and of matrix metalloproteinase 9, with the following key findings:

  • COX-2 and mPGES-1 Up-Regulation: Both 27-OH and HNE significantly increased COX-2 protein levels in the cells. Similarly, mPGES-1 mRNA levels and protein levels also rose with exposure to these oxidized lipids, particularly HNE.
  • PGE2 Production: The increased activity of COX-2 and mPGES-1 led to a corresponding surge in PGE2 production. PGE2 is a potent inflammatory mediator implicated in various stages of atherosclerosis.
  • iNOS and Nitric Oxide: Expression of inducible nitric oxide synthase (iNOS) increased as a result of 27-OH and HNE treatments; nitric oxide (NO) production also increased.
These results indicate that oxidized lipids like 27-OH and HNE can directly stimulate inflammatory pathways within arterial cells, setting off a chain reaction that promotes plaque instability.

Taking Control of Your Artery Health

The research highlights the importance of managing oxidized lipids to protect your arteries. While 27-OH and HNE are produced within the body during LDL oxidation, lifestyle and dietary choices can significantly influence this process.

Here are key strategies to consider: <ul><li><b>Antioxidant-Rich Diet:</b> Consume plenty of fruits, vegetables, and other foods rich in antioxidants. Antioxidants can help protect LDL cholesterol from oxidation, reducing the formation of harmful oxidized lipids.</li><li><b>Limit Processed Foods:</b> Processed foods often contain high levels of unhealthy fats that are prone to oxidation. Reduce your intake of fried foods, processed meats, and sugary snacks.</li><li><b>Manage Cholesterol:</b> Work with your doctor to manage your overall cholesterol levels. This may involve dietary changes, exercise, or medication if necessary.</li><li><b>Anti-inflammatory agents:</b> Natural anti-inflammatory options such as EGCG is capable of improving plaque stability.</li></ul>

By addressing the factors that contribute to oxidized lipid formation and supporting healthy inflammatory responses, you can take proactive steps to promote artery health and reduce your risk of atherosclerosis.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.freeradbiomed.2018.09.046, Alternate LINK

Title: Up-Regulation Of Cox-2 And Mpges-1 By 27-Hydroxycholesterol And 4-Hydroxynonenal: A Crucial Role In Atherosclerotic Plaque Instability

Subject: Physiology (medical)

Journal: Free Radical Biology and Medicine

Publisher: Elsevier BV

Authors: Simona Gargiulo, Daniela Rossin, Gabriella Testa, Paola Gamba, Erica Staurenghi, Fiorella Biasi, Giuseppe Poli, Gabriella Leonarduzzi

Published: 2018-12-01

Everything You Need To Know

1

What role do 27-hydroxycholesterol and 4-hydroxynonenal play in artery trouble?

Atherosclerosis involves more than just clogged arteries; it is a complex inflammatory process. The enzyme system cyclooxygenase 2/membrane-bound prostaglandin E synthase 1 (COX-2/mPGES-1) becomes overactive, leading to plaque instability and potential rupture. This overactivity is caused by oxidized lipids, such as 27-hydroxycholesterol (27-OH) and 4-hydroxynonenal (HNE) when low-density lipoproteins (LDLs, or "bad" cholesterol) become damaged.

2

How do 27-hydroxycholesterol and 4-hydroxynonenal contribute to plaque instability and inflammation?

27-hydroxycholesterol (27-OH) and 4-hydroxynonenal (HNE) promote the up-regulation of COX-2 and mPGES-1. This leads to increased production of prostaglandin E2 (PGE2) and nitric oxide. Prostaglandin E2 (PGE2) then contributes to inflammation and matrix metalloproteinase production by activated macrophages, potentially causing plaque rupture.

3

What were the key findings regarding 27-hydroxycholesterol and 4-hydroxynonenal's impact on artery inflammation?

Researchers found that both 27-hydroxycholesterol (27-OH) and 4-hydroxynonenal (HNE) cause an increase in the production of COX-2 and mPGES-1 enzymes, leading to increased PGE2 production, a molecule that promotes inflammation. Also, expression of inducible nitric oxide synthase (iNOS) increased as a result of 27-OH and HNE treatments; nitric oxide (NO) production also increased.

4

What are the broader implications of research on 27-hydroxycholesterol and 4-hydroxynonenal for understanding artery health?

The research indicates that oxidized lipids like 27-hydroxycholesterol (27-OH) and 4-hydroxynonenal (HNE) can directly stimulate inflammatory pathways within arterial cells. This stimulation sets off a chain reaction that promotes plaque instability. While the exact mechanisms are still being researched, the study highlights the importance of managing oxidized lipids to protect your arteries.

5

Can lifestyle and dietary choices really impact the effects of 27-hydroxycholesterol and 4-hydroxynonenal?

While 27-hydroxycholesterol (27-OH) and 4-hydroxynonenal (HNE) are produced within the body during LDL oxidation, lifestyle and dietary choices can significantly influence this process. By managing oxidized lipids, you can take control of your artery health. Further research will hopefully explore specific dietary interventions and lifestyle modifications that can minimize the formation of these harmful lipids.

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