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There seems to be a pervasive popular belief that cholesterol clogs the arteries, with cholesterol buildup eventually becoming so great that blood flow to the heart or brain becomes blocked, causing heart attack or stroke. Biomedical research over the past fifteen to twenty years has shattered this model of cardiovascular disease. Indeed, half of all myocardial infarctions (blood clots in the heart) occur in arteries with less than 50 percent narrowing from atherosclerotic buildup, which is considered to be only mild atherosclerosis (Smith 1996). Scientists now realize the subtle complexities of atherogenesis (development of atherosclerosis) and the life-threatening complications that arise as a consequence. The simplistic model invoked gradual deposition of cholesterol along the lining of the arteries, much like the deposition of scale and corrosion in pipes. Metal pipes carrying water through a hot-water heater may accumulate minerals to the extent that water flow becomes so restricted that little water can pass through them. This was a convenient, mechanistic representation for atherosclerotic plaque buildup and the resulting heart attack. However, our vascular system is a little more complicated than even the most sophisticated plumbing systems. Cholesterol is not causing atherosclerosis and heart disease but is being dragged into the fray by a complex cast of molecular characters. Arteriosclerosis was recognized in the nineteenth century as a vascular disease that could lead to death from heart attack or stroke. It was known that arteries became ossified, a process similar to bone formation, hence the term “hardening of the arteries.” In the 1850s the noted physiologist Rudolf Virchow described atherosclerosis as an inflammatory disease of the arterial inner layer (Libby 2000). This condition seemed to progress with age and was generally looked upon as one of the inevitable maladies of aging. Fatty deposits along the arterial lining were known to have a high content of cholesterol, in addition to fats and minerals such as calcium and phosphate. It is interesting that the 6 Atherosclerosis 73 DIETARY FATS IN HEALTH AND DISEASE 74 concept of ossification, or bone formation in the arteries, fell out of vogue in the twentieth century. It was replaced by the notion that calcium and phosphate simply precipitated in the fatty deposits—much like scale buildup in hot-water pipes. The simplistic view of passive deposition of these artery-clogging fats and minerals was probably more appealing than trying to invoke active biological processes, since the molecular and cellular events that resulted in atherosclerotic plaque were not understood. Historical developments that led to the hypothesis that cholesterol was responsible for atherosclerosis and heart disease were discussed in chapter 1. The Framingham Heart Study found a greater incidence of heart disease among people with high blood cholesterol levels, although high blood pressure, arrhythmias, and cigarette smoking also increased risk of heart disease. Several independent studies showed that saturated fats in the diet would raise blood cholesterol levels, while polyunsaturated vegetable oils would lower blood cholesterol. Today the biochemical mechanisms for the cholesterollowering effect of polyunsaturated fatty acids are known (see chapter 4). Whether a person has high or low serum cholesterol is genetically determined . Many people with high cholesterol or, more specifically, high levels of LDL (low-density lipoprotein) have a genetic predisposition for this condition (Sing and Boerwinkle 1987; Knijff et al. 1994; Eichner et al. 2002). Some individuals exhibit large fluctuations in serum cholesterol with changes in their diet, while others experience relatively little change in cholesterol levels in response to the same dietary changes—again there is probably a genetic link. Diet cannot be ignored as an important factor contributing to one’s overall health, well-being, and longevity. The modern “American” diet may be having a profound negative influence on vascular as well as other diseases. This chapter will discuss the biochemical and physiological bases for atherogenesis (development of atherosclerotic plaque) and myocardial infarction, and how dietary factors, specifically polyunsaturated fatty acids, influence these processes. There are several factors that are good indicators of heart disease risk (discussed in chapter 7); serum cholesterol, or more specifically LDL-cholesterol, is only one of them. However, LDL is the major factor in promoting atherosclerosis , yet cholesterol in the LDL particles has very little to do with it. A Changing Paradigm of Atherogenesis Several decades ago it was recognized that fat deposits are formed by a specialized group of white blood cells known as macrophages that become lodged in the space between endothelial cells, which form the lining...

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