 Modification of the lipoproteins occurs by oxidation. Lipoproteins, mainly LDLs with a high cholesterol content and very low-density lipoproteins (VLDLs), are oxidized by chapter 13 Cardiovascular System  GENERAL FEATURES OF ARTERIES AND VEINS 411 Atherosclerotic lesions are the most common acquired abnormality of blood vessels. More than half of the annual deaths in the United States are related to complications of atherosclerotic disease, which includes  ischemic heart disease (see Folder 13.3), myocardial infarction, stroke, and gangrene of the limbs. Lesions develop pri-marily in the tunica intima of large elastic arteries follow-ing endothelial injury, which leads to endothelial dysfunction. Factors that predispose to endothelial in-juries include low-LDL cholesterol hyperlipidemia, hyper-glycemia (in diabetes), hypertension, increased toxin levels associated with cigarette smoking, and certain viral and bacterial infections caused by cytomegalovirus (CMV) or Chlamydia pneumoniae, respectively. Altered function of vascular endothelium leads to increased per-meability to LDL cholesterol and increased adherence of white blood cells to the endothelium. Endothelial injury in-creases the production of reactive oxygen species such as O2 , H2O2, OH, and ONOO, which in turn oxidize LDL in the tunica intima of the artery. In response to this injury, monocytes from the bloodstream enter the tunica intima and differentiate into macrophages. Macrophages phagocytize oxidized LDL, slowly transforming themselves into foam cells with a characteristic spongy appearance of the cytoplasm loaded with lipid-containing vesicles. Foam cells and infiltrated T lymphocytes form the initial atherosclerotic lesion, or fatty streak. This lesion under-goes further remodeling and growth into fibrofatty plaque as smooth muscle cells migrate from the media and fibrob-lasts form a protective capsule of connective tissue (Fig. F13.1.1). A thick layer of fibrous connective tissue con-taining scattered smooth muscle cells, macrophages, foam cells, T lymphocytes, cholesterol crystals, and cell debris is known as an atheromatous plaque. Progression of the plaque is marked by accumulation of lipid and loss of integrity of the endothelium. In advanced lesions, blood stasis and clotting (thrombosis) may lead to occlusion of the vessel. Other changes seen in advanced lesions in-clude thinning of the tunica media, calcification of accu-mulated extracellular lipids, and necrosis within the lesion (Fig. F13.1.2ab). Progression from simple to complicated lesions can be found in some people as early as their 20s and in most individuals by age 50 or 60 years.
 FOLDER 13.1 Clinical Correlation: Atherosclerosis