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.