Editor’s Note: This piece was originally published in our May 2002 issue. We are posting it because of news from the JUPITER trial.

AS RECENTLY AS FIVE YEARS AGO, most physicians would have confidently described atherosclerosis as a straight plumbing problem: Fat-laden gunk gradually builds up on the surface of passive artery walls. If a deposit (plaque) grows large enough, it eventually closes off an affected “pipe,” preventing blood from reaching its intended tissue. After a while the blood-starved tissue dies. When a part of the cardiac muscle or the brain succumbs, a heart attack or stroke occurs.

Few believe that tidy explanation anymore. Investigations begun more than 20 years ago have now demonstrated that arteries bear little resemblance to inanimate pipes. They contain living cells that communicate constantly with one another and their environment. These cells participate in the development and growth of atherosclerotic deposits, which arise in, not on, vessel walls. Further, relatively few of the deposits expand so much that they shrink the bloodstream to a pinpoint. Most heart attacks and many strokes stem instead from less obtrusive plaques that rupture suddenly, triggering the emergence of a blood clot, or thrombus, that blocks blood flow.

The research has, moreover, established a key role for inflammation in atherosclerosis. This process—the same one that causes infected cuts to become red, swollen, hot and painful—underlies all phases of the disorder, from the creation of plaques to their growth and rupture. When microbial invaders threaten to hurt us, inflammation (literally meaning “on fire”) helps to ward off infection. In the case of atherosclerosis, though, the inflammation proves harmful. In other words, our own defenses bombard us with friendly fire, just as happens in more famously inflammatory conditions, such as rheumatoid arthritis.

This revised conception suggests new ideas for detecting and treating atherosclerosis. It also resolves some disturbing mysteries—notably, why many heart attacks strike without warning and why certain therapies meant to avert heart attacks frequently fail. Society sorely needs advances in prevention, detection and therapy of atherosclerosis. Contrary to public perception, the heart attacks and strokes that result from this condition exceed cancer as a cause of death in industrial nations and are growing more prevalent in developing countries as well.

Igniting Trouble
LACKING TOOLS to describe interactions among cells and molecules, the ancients who first defined inflammation had to focus on what they could see and feel. Today we know that the outward signs reflect a pitched struggle playing out on a microscopic battlefield. After sensing (rightly or wrongly) that a microbial attack has begun, certain white blood cells— the immune system’s frontline warriors— convene in the apparently threatened tissue. There they secrete an array of chemicals intended to limit any infection. These chemicals include oxidants (able to damage invaders) and signaling molecules, such as small proteins called cytokines, that orchestrate the activities of defensive cells. Researchers therefore document an inflammatory response by identifying inflammatory cells or mediators of their activities in a tissue.

The clearest picture of inflammation’s role in the onset of atherosclerosis comes from investigations into low-density lipoprotein, a.k.a. bad cholesterol. LDL particles, composed of fatty molecules (lipids) and protein, transport cholesterol (another lipid) from their source in the liver and intestines to other organs. Scientists have long known that although the body needs LDL and cholesterol, excessive amounts promote atherosclerosis. Until recently, however, no one could explain how a surplus leads to plaque formation.

4 Comments

1. 1. Steven Brown 02:41 AM 11/14/08

   Linus Pauling wrote in 1986 that vitamin C decreases LDL and increases HDL in the blood. C binds to cholesterol and transports it to the liver, where it is converted to bile and excreted. Vitamin C is a component of collagen, an essential structural component of arteries. Dr. Pauling wrote that atherosclerotic plaque is an evolutionary adaptation to the chronically low levels of vitamin C in humans, one of the few species who do not synthesize vitamin C internally. The medical-pharmaceutical establishment does not advocate vitamin C to prevent heart disease because there is far greater profit in treating heart disease, by means of medical procedures and drugs.

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2. 2. David Gortler 05:03 PM 1/30/09

   Although most people don’t realize it, atherosclerosis is a disease which, in addition to being a lipid storage disorder, also has components of inflammatory and immunologic disease. Thanks to television commercials, the cartoon image of cholesterol plaques that most people have in their head is if a yellow cholesterol plaque stuck to a red arterial wall. The truth is that most of that yellow plaque is not make up of cholesterol; it is made up of the body’s own cells responding to an endothelial disturbance, in addition to cellular markers of inflammation such as TNF-a, IL-6, hsCRP, foam cells, among many others. One of the main differences in the effectiveness of HMG CoA reductase inhibitors or “statins” in addition to their ability to increase the metabolism of cholesterol, is their ability to decrease inflammation. The two drugs that are best at decreasing inflammation cholesterol metabolism are Lipitor (atorvastatin) and Crestor (rosuvasatin). No currently marked drug exists which can affect the immunologic or cell migration effect in atherosclerotic plaques.

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3. 3. Maria Ines Azambuja 05:32 PM 5/3/10

   I suggest a new round of actualization now in 2010. Influenza would sure receive more consideration today regarding myocardial infarction triggering. But I continue to insist that triggering not its sole contribution.
   
   Maria Ines Azambuja, MD
   see Connections Braz J Med Biol Res January 2008, Volume 41(1) 1-4

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4. 4. Wilmark 10:28 PM 10/17/12

   I came to this article to see what a respected institution had to say about the causes of Atherosclerosis. The lipid theory has been significantly discredited by most research untouched by big pharma. This piece while not directly advocating it is pointing to statin therapy, and relating Atherosclerosis to LDL levels. When research said that there is no difference amongst patients who have had a heart attack in terms of their cholesterol levels - the proponents say we need to lower the LDL threshold, despite the almost total lack of evidence that LDL serum levels have anything to do with MI. What is disappointing is that there is NO discussion about what causes the inflammation in the first place. The levels of MI in our society have increased steadily in the past 100 years or so. These breakthroughs (in statin therapy) have not provided any solution to this health issue. The key is understanding lies in what causes the inflammation that leads to Atherosclerosis and modifying our lifestyle and diet to suit. The information must be there somewhere - there is somehting that has changed in the past 100 yrs that have made this MI epidemic, but maybe its not in the interest of some stakeholders for us to find out. Unfortunately SA have added more fuel to the old song about cholesterol myth and I await patiently when this Stalin billion dollar scam blows open.

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