In his article titled “Atherosclerosis: The New View”, Peter Libby states that the proposition that atherosclerosis is an inanimate pipe problem due to fat deposits on the arterial walls is no longer tenable. This is supported by research that began almost 20 years ago, which suggests that inflammation, the natural process in the body that helps us ward off infection is the key/central player in plaque formation in atherosclerosis, and that plaque deposits form within arterial walls, and not on them. Also in his article, Libby details the step-by-step process of plaque formation, the consequences, and his suggested methods of treatment. But to contrast from previous beliefs of the disease formation, he states that:

  • Arteries are not inanimate pipes, rather they contain numerous living cells within them that communicate constantly with one another and their environment. At this point it should be noted that there are three layers of an arterial wall; tunica adventitia, which is the outermost layer containing collagen fibres, tunica media, which is the middle layer containing smooth muscle cells and elastic fibres, and the last layer is tunica intima, the innermost layer of an arterial wall containing endothelium cells.
  • Plaque deposits occur in vessel walls, not on them. This is because, vessel walls participate in the development and growth of atherosclerotic deposits, as it will be discovered further in the next section that details the stages of plaque formation.
  • Another key player in the formation of atherosclerosis are low-density lipoproteins (LDLs). LDLs have been considered by many as “bad cholesterol”, which is rightly so. These lipoproteins are composed of fatty molecules (lipids) and protein that help transport cholesterol from the liver and intestines to other organs. But some scientists have suggested that a surplus of these LDLs may lead to plaque formation.

atherosclerosis by peter libby

 The Five Stages of Plaque Formation

Birth of A Plaque

  1. LDLs take cholesterol from the liver and intestine reserves into the bloodstream to be transported to other body organs. During this process, excess LDLs may latch onto the initima (tunica intima – innermost layer containing endothelium cells) in the arterial walls, which is the part closes to the bloodstream. During normal circumstances, LDLs typically pass in and out of the intima without any problems. However, in excess, LDLs become stuck in the initima and begin to accumulate. As the LDLs accumulate, their fatty molecules (lipids) undergo oxidation, and the body misinterprets this chemical alteration as an infection. The body eventually sends defense chemicals/cells to ward the supposed infection. These defense cells include monocytes, T cells, and chemokines.
  2. The presence of chemokines may induce the monocytes to multiply and mature into active macrophages. These macrophages display molecules called scavenger receptors on their outer surface. Scavenger receptors help capture modified LDL particles and help the macrophages to ingest these LDLs.
  3. Upon ingestion of excess LDL particles, macrophages become very packed with LDL particles known as fatty droplets, and appear foamy. Appropriately, pathologists have now named these fat-filled macrophages as foam cells. These frothy looking, fat laden macrophages (foam cells) and T cells constitute the fatty streak, which is often referred to as the earliest form of atherosclerotic plaque.

Plaque Progression

  1. This is often termed the healing process, because typically, once an inflammation occurs in the body system, even at the cellular level, restoration back to the original body state eventually follows. However, in the case of atherosclerotic plaque formation induced by inflammation, artery walls do not return to their original state, rather remodeling occurs, which often leads to an even bigger and more complicated plaque located and visible on arterial walls. In this fourth stage of plaque formation, inflammatory molecules promote plaque growth by forming a fibrous core over the already formed lipid core (formed in stage 3). A cap develops when the endothelial cells and macrophages in the tunica intima promote the smooth muscle cells in the tunica media to migrate to the top of the intima in order to multiply and produce a tough, fibrous matrix that glues the cells together to become a fibrous cap. This cap covers the atherosclerotic zone and walls it off safely from the blood. However, once the cap has been formed, the plaque/atherosclerotic zone (zone present underneath the fibrous cap) eventually dies and release lipids and inflammatory substances in order to become a necrotic core.

Plaque Rupture

  1. In this final stage, some inflammatory substances released from the necrotic core may weaken the fibrous cap by digesting matrix molecules and damaging smooth muscles that then fail to repair the perforated fibrous cap. Thus, plaque rupture initiates when the fibrous cap weakens and breaks, which often promote blood to sip through the cap rupture/breakage. Since foam cells may display tissue factor (i.e. a potent clot promoter), this tissue factor will interact with the blood and other clot promoting elements in the blood to form a clot (or thrombus) over the breakage in the cap. If the clot is large enough, blood flow to the heart may be altered from the inflamed (affected) artery and heart attack, cardiac tissue death, and stroke may occur. It should be noted that the body can prevent excessive clot growth but due to the fibrous cap breakage, the necrotic core releases substances that alter the cessation of clot formation.

 Thoughts & Opinion

            After analyzing Libby’s article, it is evident that his theory on inflammation being the central player in atherosclerotic plaque formation appears plausible. A correlation between inflammation and atherosclerosis appears evident perhaps because of Libby’s rich description of the underlining cellular mechanism that drives plaque initiation and growth. Libby’s theory then begs the question, is plaque formation reversible? And that perhaps there may now be a cure or a more effective management regimen for patients with atherosclerosis. This revised conception postulated by Libby also suggests new ideas for detecting and treating atherosclerosis and resolves some mysteries – notably why certain heart attacks strike without warning and why certain therapies aimed to avert heart attacks frequently fail. Therefore, upon analyzing Libby’s article, can we then determine that we have arrived a new age that assures us of a cure for atherosclerosis and that perhaps certain new drug designs may become effective if they focus on targeting the key player in atherosclerosis, i.e. can an anti-inflammatory drug designed to alter plaque growth be effective? And that can the excess LDLs that initiate plaque formation be counteracted with excess High Density Lipoproteins – HDLs (the good lipoproteins)? Society needs advances in prevention and there is no doubt that Libby’s article promises advancement towards atherosclerosis prevention.

Read Peter Libby’s article titled “Atherosclerosis: The New View