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The human circulatory system functions as two pumps in series that send blood throughout the body in a highly dynamic system of distributing and collecting ducts. The circulatory system serves to transport essential substances to and remove waste products from tissue. Additionally, the circulatory system plays a critical role in body temperature, humoral communication, and complex regulation of oxygen homeostasis in a wide variety of physiologic states. This chapter seeks to elucidate common disease processes of the cardiovascular system.



Despite major advances in cardiovascular medicine and preventative services, atherosclerosis remains the leading cause of morbidity and mortality in developed nations.1 Through its major manifestations, myocardial infarction (MI) and stroke, atherosclerosis is also a major health burden in developing nations. Atherosclerosis is a chronic arterial disease that has a latency of many years and is often found in the context of medical comorbidities such as diabetes or hypercholesterolemia. In order to understand the pathophysiology of atherosclerosis we will first review normal anatomy and physiology of the artery wall.

Review of Normal Vascular Wall Anatomy Function

The arterial wall is comprised of three layers: the tunica intima, tunica media, and tunica externa (e.g., adventitia). The tunica intima is formed by the innermost layer of the blood vessel where it forms a metabolically active continuous cellular lining of the cardiovascular system. In a healthy artery the tunica intima is comprised of a simple squamous cellular lining, basement membrane, and internal elastic lamina which functions to demarcate the tunica intima from the muscle cells of the tunica media. One major responsibility of the tunica intima is to regulate fibrinolysis via glycosaminoglycans (i.e., heparan sulfate), plasminogen activators, and thrombomodulin lining the luminal endothelial surface.2 The intima also secretes nitric oxide (NO) and prostacyclin (PGI2) as circulating modulators of clot formation. Moreover, the intima is a critical regulator of the immune response by inhibiting leukocyte adhesion and migration through the vessel wall in the absence of inflammatory stimuli.3 Next, the tunica media forms the thickest layer of the arterial wall confined on either side by the internal elastic laminae and external elastic laminae. The external elastic boundary separates the tunica externa from the tunica media. Tunica media is entirely made up of smooth muscle cells and extracellular matrix which provide forceful contraction and dilation of the vessel lumen to alter blood flow and pressure. Of note, smooth muscle cells synthesize and recycle the collagen, elastin, and proteoglycans which compose the extracellular matrix.4,5 Lastly, the adventitia is the outermost layer of the artery wall that can be subdivided into an inner compact layer and an outer loose connective layer. The adventitia contains nerves termed the nervi vasorum and blood vessels termed vasa vasorum that ultimately nourish and protect the inner cells of the artery wall.6

Atherosclerotic Arterial ...

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