Nov 18, 2009

Paper Analysis

The Importance of a Substantial Elastic Lamina Subjacent to the Endothelium in Limiting the Progression of Atherosclerotic Changes

F.H.Sims, X.Chen & J.B.Gavin


Atherosclerosis is a disease that plagues the human population as a result of so many different factors that it is often difficult to analyze pathological change. With such issues as diet, lifestyle and genetics causing the disease, it is often complicated to pinpoint the one critical deciding factor. Endothelial damage has long been considered to be a pivotal determinant in the development of atherosclerosis. The authors of this paper decided to compare a vessel that has a naturally low occurrence of atherosclerosis, the internal thoracic artery, to a vessel that typically begins to experience plaque deposits at an early age, the anterior descending branch of the left coronary artery. By doing so, the structural importance of the internal elastic lamina in larger pulsatile arteries can be demonstrated. Past studies have revealed that intimal thickening only arises in these vessels when there are defects in the internal elastic lamina. The elastic lamina, formed by mesenchymal originating cells such as fibroblasts, smooth muscle cells and endothelium, is typically very stable. This experiment desired to follow the advancement of intimal thickening to atherosclerosis and how it may be linked to the improper maintenance of an adequate elastin membrane beneath the vessel endothelial cells.


This experiment histologically sampled 687 human coronary arteries and 293 human internal thoracic arteries post-mortem from 5 different ethnic backgrounds to avoid race related anomalies in data collection. Blocks of tissue from a wide range of ages were then fixed, embedded, sectioned and stained with hematoxylin and eosin for easy microscopic observation. Measurements were made of the lumen diameter as well as the thicknesses of the media and intima layers using a calibrated eye piece. A simple calculation of mean intimal thickness divided by media thickness represented intimal thickening and these results were tabulated according to the age group of the studied individuals. The integrity of the barrier at the luminal surface of the intima was determined through electron microscopy and immunoperoxidase staining for the diffusion of macromolecules from the plasma into the arterial wall.


The results obtained in this experiment for the internal thoracic artery were as follows. In newborn subjects, the inner surface of the media was lined by a well formed thick internal elastic lamina that was covered by a continuous layer of endothelial cells. Early in life, a separation of the endothelium from the internal elastic lamina and the occasional smooth muscle cell appearing in the intimal compartment were observed. In the first decade of life, the internal elastic lamina became both thicker and continuous but remained largely unaltered for the remainder of life. While the endothelial cells of the arterial wall prevented blood lipid and macrophages from entering the intimal compartment, the coronary arteries did not display the same barrier function. Amongst individuals there were occurrences of extensive defects to the internal elastic lamina and endothelial separation. These areas were synonymous with intimal thickening as well as penetration by macrophages. Where advanced intimal thickening was observed, the intima was very similar to its condition when coated with atherosclerotic plaque. Within the same individual, the amount of intimal thickening in the internal thoracic artery was notably less than that observed in their coronary artery.

In the coronary artery, changes occurred earlier and at a higher intensity than in the internal thoracic artery. From birth to approximately ten years of age, the intima became populated by smooth muscle cells. From ten to thirty years of age, a large increase in lipid and macrophage content in the intima was noted in areas associated with greater intimal thickening. Past the age of thirty, the formation of vessel wall clots occurred in areas already subjected to thickening. A greater amount of birth defects were noted in the coronary arteries, mostly in the continuity of the elastic lamina and the distribution of endothelial cells. Smooth muscle proliferation in the intima early in life occasionally resulted in an incomplete endothelial layer and a decreased amount of elastin. Lipid and macrophage introduction into the intimal compartment was much greater in thickened regions and appeared to further accentuate the thickening. In later years of life, the coronary arteries show great plaque build up in areas of thickened intima which trap blood cells in a matrix of collagen and fibrin while showing a decrease in luminal barrier ability.

Based on the collected data and observations, the researchers deduced that the main factor in intimal thickening and atherosclerosis is the integrity of the barrier between blood and the arterial wall. Intimal thickness was also found to be correlated with defects of the elastic lamina which was typically congenital. Secure attachment for the cells and a protective barrier to the intima is made possible by a complete elastin membrane subjacent to the endothelial cells. Separation of the endothelium from the internal elastic lamina and the migration of smooth muscle cells in the intima resulted in an attempt to reform the elastin membrane, the outcome of which determined subsequent events. Successful formation of the elastic lamina has been shown to prevent an influx of macrophages and lipids to the intimal compartment minimizing intimal thickening which progresses to atherosclerosis. A loss of endothelial cells coupled with a weak elastin membrane has been shown to be strongly correlated with the formation of atherosclerotic plaque. The researchers concluded that an increase in intimal thickening is difficult to stop but controlling lipid and macrophage levels reduces the chance of lesions and promote a more uniform thickening with less possibility of atherosclerotic plaque build up.


In a critical analysis of this publication, the researchers provided sound data obtained through practical methods. As the experiment involved merely measuring the widths and diameters of vessel characteristics, a simple methods regimen of using microscopy and a calibrated eye piece as well as a general stain that allows proper measurement was both appropriate and successful. The goal of the experiment was to show a correlation between elastin membrane condition and the onset of atherosclerosis and intimal thickening. Indeed, the data collected agreed with this hypothesis and the experimenters followed through well on explaining the relevance of the numbers and ratios in understanding that a thickening of the arterial wall can progress to atherosclerotic conditions. Previous studies were periodically cited; inferring that prior research had been conducted and that their results were being critically compared to scientifically accepted academic papers. Figures provided in the paper were very useful in further understanding of the topic. One tragic realization upon reading this paper is the fact that nearly all of the arteries that had the greatest potential for future disease were congenitally afflicted. The paper concludes with stressing methods that can aid in the prevention of plaque build up such as reducing dietary consumption of animal fat and total caloric intake.

This paper, however, does not offer any supplemental anatomical discussion in the introduction. Had a reader not been properly educated, no explanations of blood vessel function or a broad overview of general vessel histology and anatomy would have made the paper very confusing, especially due to its repetitive nature. Further questions may also be raised over how the data was obtained. In the materials and methods section, it was stated that coronary and thoracic vessels of the same individual would be compared and subjected to calculations prior to submission to the overall results; however, the experiment used an unequal number of each form of vessel (293 thoracic vessels compared to 687 coronary arteries) meaning they all could not have possibly been paired and contrasted. Despite race being accounted for, factors that were not mentioned in the samples were the genetics, lifestyle and socioeconomic status of the individuals studied which could have had a major impact on the individual’s development of cardiovascular disease. Overall, I feel that this paper provides results that accomplished its goals, the clear analysis required for a full understanding, and data that must be critically considered.

Oct 26, 2009

The Coronary Arteries

The human heart is one of the most extraordinary tools employed for use in the body and has been perfected through evolution. Continuously pumping throughout its entire life, the heart supplies the body with a constant supply of blood and the payload which it carries. Oxygen, nutrients, hormones and countless other compounds are delivered via blood circulation throughout the body while cellular wastes are conversely deposited into returning blood flow for disposal. The muscular pumping action of the myocardium is dependent on a steady supply of oxygen just like any other muscle tissue and therefore requires a blood supply itself. The required distribution of blood to the myocardium is facilitated by the coronary arteries.

Despite the lumen of the heart being filled with blood for the majority of its life, nutrients and oxygen cannot be obtained by myocardial cells without the assistance of the coronary arteries. The cellular arrangement of the heart is very closely packed which does not permit blood flow directly among the myocardial muscle cells which therefore remain deoxygenated (Hill, 2008). Coronary circulation is carried out by the coronary arteries which branch from the base of the systemic aorta and carry freshly oxygenated blood to capillary beds within the myocardium before exiting to the right atrium via the coronary veins (Hill, 2008). This coronary circulation must deliver oxygen at a high resting rate in response to high myocardial demand as these cells typically require more than 20 times greater amounts of oxygen than resting skeletal muscle (Levick, 2003).

There are two coronary arteries, left and right, that originate from the right and left aortic sinuses (Fuster, 2004). The right artery travels along the coronary sulcus embedded in adipose tissue between the right atrium and towards the apex (Fuster, 2004). Branches from the right artery extend to the atrial myocardium, atrial septum, right ventricle, ventricular septum and the left ventricle (Little, 1989). The pulmonary conus and atrioventriuclar node of the heart may be supplied by either the right coronary artery or an alternate branch (Little, 1989). The left coronary artery divides into two branches termed the left circumflex artery and the left anterior descending artery which travel through adipose tissue with the latter manoeuvring through epicardial fat (Fuster, 2004)). The left anterior descending artery does as its name implies and travels downward towards the apex supplying blood to the left ventricle, ventricular septum and the right ventricle (Little, 1989). The left circumflex artery extends through the atrioventricular sulcus between the left atrium and ventricle which are both the main recipients of oxygenated blood from this branch (Little, 1989). Many structures of the heart are nourished by branches of both the left and right, unequally however, as dominance is displayed by the right coronary artery in 70% of all cases (Fuster, 2004). Despite the importance of the coronary arteries, circulation in this region is the shortest in the body with a mere 6-8 second cycles (Levick, 2003).

The walls of the coronary arteries have three layers termed the tunica intima, tunica media and tunica adventitia. The innermost layer, the intima, consists of a sheet of simple squamous endothelial cells which rests upon connective tissue and a thin basal lamina (Levick, 2003). This layer functions to secrete vasodilators such as nitric oxide and acts as a barrier which prevents the loss of plasma (Levick, 2003). The middle media layer contains circumferential smooth muscle cells spread through a matrix of elastin and collagen for contractile and mechanical strength (Levick, 2003). Signals may be conducted between the intima and media layers via endothelial cells that project through elastic lamina to contact smooth muscle cells (Levick, 2003). Fenestrations in the elastic lamina layers allow for the diffusion of nutrients and oxygen from the blood into the tunica media. The elastin content of the media layer allows the walls of the coronary arteries to stretch during cardiac ejection, resisting blood travelling at very high pressures (Mohrman, 2006). The outer connective tissue sheath that functions to keep the vessel loosely attached to surrounding tissue is termed the adventitia, consisting of mostly type one collagen, anchoring elastic fibres and a vasa vasorum network of smaller vessels (Levick, 2003). The coronary arteries consist of a relatively thick tunica media with a large amount of smooth muscle which functions to prevent collapse (Levick, 2003). This thick layer of muscle contracts and relaxes regularly due to autonomic innervations resulting in vasoconstriction or vasodilation respectively (Levick, 2003).

Angiogenesis, the formation of new vessels, occurs for many reasons including fetal development, tissue growth or adaptation and the growth of cancerous tumours (Levick, 2003). Endothelial growth is initiated by vascular endothelial growth factor as well as acidic and basic fibroblast growth factors (Levick, 2003). These growth factors are highly concentrated in tissues that form new vessels such as tumours and fetal tissue (Levick, 2003). Through a cascade of enzymatic reactions, these growth factors result in the activation of angiogenesis transcription genes (Levick, 2003). Endothelial basement membrane is degraded which is followed by the off-shooting of endothelium from existing vessels (Levick, 2003). The lumen of the vessel is created as vacuoles form within the cell interior as cells divide and migrate, lengthening the developing artery (Levick, 2003). Newly formed vessels are highly permeable and allow the vast influx of fibrinogen which forms an extensive fibrin vascular matrix termed the granulation tissue (Levick, 2003). Simple endothelial tubes are created which eventually differentiates into an artery, vein or capillary (Levick, 2003). In the developing embryo, both coronary endothelial and smooth muscle cells derive from a cluster of cells adjacent to the sinus venosus of the heart called the pro-epicardium organ (Fuster, 2004).

Problems may arise in the functioning of the coronary arteries and the results can accentuate how critical these vessels are to life. When the blood flow in the coronary arteries fails to meet the oxygen requirements of the myocardium, the pumping efficiency of the heart declines. The most common form of coronary artery disease is atherosclerosis in which lipid plaque deposits amass on the lumen of the vessel and potentially become calcified as well (Mohrman, 2006). The build up of plaque significantly narrows the lumen of the arteries which can increase the usually low vascular resistance, promote clot formation through aggregation of platelets and potentially close off the artery all together (Mohrman, 2006). Apart from restricted cardiac output, atherosclerosis can cause heart attacks or strokes when the hardened plaques fragment and metastasize in other important bodily vessels (American Heart Association, 2009). Damage to the endothelial lining caused by tobacco smoke, diabetes, physical inactivity, obesity, high blood pressure and high LDL blood cholesterol levels increase the risk of severe atherosclerosis (American Heart Association, 2009). When the strong contractions of the coronary tunica media are intense and prolonged or narrow arteries undersupply oxygen to myocardial cells, pain results as in the condition angina pectoris (Levick, 2003). While not a disease itself, angina is the most common symptom of coronary artery disease (National Heart Lung and Blood Institute, 2007).

There are several methods to combat the aforementioned pathologies. Behavioural and dietary changes can aid in the prevention or even reversal of coronary artery disease. As many of the causes of this disease are lifestyle choices, quitting smoking, regular exercise and decreasing blood lipid (especially LDL cholesterol) levels through diet or pharmaceuticals can result in improved coronary conditions. Drugs that alter the functioning of the vessels also act to treat coronary artery disease. Vasodilators, such as nitroglycerin or calcium channel inhibitors, expand the diameter of the vessel lumen and permit more blood flow (Mohrman, 2006). Other drugs, such as propranolol, may act to limit myocardial oxygen consumption and act on cardiac sympathetic nerves to prevent an increase in heart rate above what the coronary blood flow can sustain (Mohrman, 2006). Alternative surgical treatments are available as well in the management of coronary artery disease. In angioplasty, a balloon tipped catheter is fed through the vessels and rapidly inflated at strategic points as to compress plaque build up against the vessel wall (Mohrman, 2006). Often implanted at the same time as angioplasty is performed, a rigid device called a stent is left in the vessel and acts to prop it open which increases blood flow (Mohrman, 2006). A more invasive operation, coronary bypass surgery, may also be performed if the other methods are unsuccessful. In this surgery, blood vessels from the patient’s own body (such as a mammary artery) or a synthetic vessel are transplanted to provide an alternate route for blood flow (Mohrman, 2006). The artery originates prior to and inserts just after a blockage, providing a parallel low resistance passage for blood (Mohrman, 2006).

The coronary arteries form a critical lifeline for one of the most important organs in the body. These vessels are heavily depended upon by the heart but are highly specialized enough to keep up with the demand. When these nourishing structures do not receive the necessary care they require, problems may arise and a lifetime of perpetual service can suddenly cease.


American Heart Association (2009). Atherosclerosis. Retrieved 15 October 2009 From:

Community Memorial Hospital (2009). The Working Heart: Coronary Arteries. Retrieved 15 October 2009 From:

Fuster, Valentin, et al. Ed. Hurst’s The Heart. Vol. 1. New York: McGraw-Hill Medical Publishing Division, 2004. 2 vols.

Genentech. Tissue Growth and Repair. Retrieved 13 November 2009 From:

Hill, Richard W., Gordon A Wyse, and Margaret Anderson. Animal Physiology. 2nd Ed. Sunderland: Sinauer Associates Inc., 2008.

Intensive Care Coordination and Monitoring Unit (2007). Coronary Artery Bypass Graft. Retrieved 15 October 2009 From:

Levick, JR. An Introduction to Cardiovascular Physiology. 4th Ed. London: Arnold Publishers, 2003.

Little, Robert C., and William C Little. Physiology of the Heart and Circulation. 4th Ed. Chicago: Year Book Medical Publishers Inc., 1989.

Mohrman, David E., and Lois Jane Heller. Cardiovascular Physiology. 6th Ed. New York: Lange Medical Books/McGraw-Hill, 2006.

National Centre for Biotechnology Information (2004). Coronary Artery Disease. Retrieved 15 October 2009 From:

National Heart Lung and Blood Institute. How are Stents Placed. Retrieved 13 November 2009 From:

National Heart Lung and Blood Institute (2007). What is Angina?. Retrieved 15 October 2009 From:

National Heart Lung and Blood Institute (2009). What Is Coronary Artery Disease?. Retrieved 15 October 2009 From:

Society for Biomaterials Special Interest Group. Cardiovascular Biomaterials. Retrieved 13 November 2009 From: