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Objectives: This study was undertaken to examine the relation of in vivo low density lipoprotein (LDL) oxidation and other lipid risk factors to coronary reactivity in normal subjects., Background: Experimental studies have shown that oxidized LDL (ox-LDL) particles are injurious to the vascular wall by impairing its normal vasodilator function., Methods: We used noninvasive positron emission tomographic (PET) imaging with intravenous dipyridamole to measure coronary flow reserve, a marker of coronary endothelial and smooth muscle function, in 30 healthy men (mean [+/-SD] age 34.4 +/- 3.2 years). As a marker of in vivo LDL oxidation, the autoantibody titer against ox-LDL was measured by the enzyme-linked immunosorbent assay method., Results: Plasma levels of autoantibody titer against ox-LDL were inversely associated with coronary flow reserve (r = -0.42, p = 0.023). High LDL cholesterol levels (above median > 3.0 mmol/liter) were associated with a low coronary flow reserve only in subjects expressing simultaneously high levels of ox-LDL titer (above median). Subjects with simultaneously high levels of LDL cholesterol and ox-LDL titer had lower coronary flow reserve values than subjects in other groups (3.89 vs. > 5.0 in other groups, p = 0.066)., Conclusions: These data provide evidence for the role of ox-LDL in affecting the coronary reactivity in vivo and support the concept that oxidative modification of LDL particles provides a mechanism by which high LDL concentrations exhibit injurious effects on the coronary vascular bed.

Narrowings of the coronary arteries were measured in 94 infants aged less than 1 year who died in hospital and 102 1- to 16-year-old children who died accidentally. The arteries were transformed mathematically to circles. The degree of narrowing caused by intimal thickening was determined as the ratio of intimal area to the original luminal area. This ratio was further transformed to percentage. The degree of narrowing varied between 0 and 58% (mean 20%). The mean degree of narrowing in the left coronary artery during the first year of life was 17% and, between 12 and 15 years, 34%. Narrowing was greater in males (P = 0.02), when all the 333 coronary samples were included in the analysis. The birthplaces of the subjects' grandparents were traced from population registers and it was found that narrowing in the left coronary artery of infants was greater in those descended from grandparents from eastern Finland, an area of high mortality from coronary heart disease (CHD). Intimal thickening in infants and children seems to be a morphological manifestation of hereditary predisposition to CHD.

Coronary arteries of 93 clinically healthy Finnish children of both sexes were collected from successive, medicolegal autopsies of victims of violent death. In the histological and histochemical study, local, cushion-type thickenings of the coronary walls were demonstrable in 47, i.e. 50 per cent, of the children, the occurrence increasing with age. The most prominent change was the splitting of the internal elastic membrane and the accumulation of smooth muscle cells, forming a new, musculo-elastic layer. Glycosaminoglycans appeared in the luminal parts of the thickenings. There was an average decrease in the succinate dehydrogenase reaction in the cushion area, implying a degenerative process. The increase in the reaction of "injury markers", acid phosphatase and esterase based on the increase of cells rich in these enzymes, indicated pathologic process. It was concluded that change of this kind, demonstrable early in childhood, may dispose coronary arteries to atherosclerosis.

Glycosaminoglycans (GAGs) were studied in normal and atherosclerotic coronary arteries of 15- to 60-year-old Finnish men who had died accidentally. The GAGs were fractionated and quantified with electrophoretic techniques. The contents of sulfated GAGs (micrograms/cm2 vessel surface area) increased continuously until 20 to 30% of the vessel surface area was covered with fibrous plaques, after which they started to decrease. The largest increases were seen in chondroitin sulfates A and C and dermatan sulfate, the former of which rose earlier with lesion development. In normal coronary arteries the contents of dermatan sulfate and chondroitin sulfates A and C increased significantly with age, but the rises were much smaller than those found in affected vessels. The age-related changes in the percentage composition of GAGs in normal coronaries were qualitatively similar to those found in affected coronaries during lesion development. The alterations in arterial GAGs, therefore, seem to be related to two processes, both of which involve increased formation of connective tissue components by arterial smooth muscle cells: the normal growth and maturation of the vessels with a slow development of diffuse intimal thickening, and atherogenesis, which greatly increases the contents of sulfated GAGs in affected arteries.

Three methods of expressing the results of biochemical analyses of normal and atherosclerotic human coronary intima-medias were compared by calculating the results per unit area of vessel surface to obtain the content, per unit weight of dry defatted tissue (d.t.) to obtain the concentration, and per unit weight of organic d.t. to obtain the inorganic salt-corrected concentration. The content reflects the amount of a substance in an anatomically defined portion of the arterial wall, whereas the concentration gives the amount of the substance relative to a defined mass of arterial tissue. Since calcium salts form a sizable portion of fibrous plaques, concentrations become overcorrected in the oldest age groups. For example, there was an unexpected age-related decrease of collagen concentration in fibrous plaques-containing coronary arteries while its content and inorganic salt-corrected concentration increased. In studies involving arterial biochemical analyses it is appropriate to calculate the results in terms of both the content and the concentration. If severely affected specimens are studied, it is recommendable also to use the inorganic salt-corrected concentration, especially when different age groups are compared with one another.

To study the early features of atherosclerosis, we analyzed coronary artery intima medias from 63 boys and 30 girls who were newborn to 15 years old at the time of accidental death. Fatty streaks were found in five boys and one girl and, with one exception, were not present until the second decade of life. From birth there was a continuous increase in esterified cholesterol (EC) and a two- to threefold rise in free cholesterol and phospholipid. DNA, total protein, and collagen tended to rise after the first decade. The content of hyaluronic acid remained fairly constant, but sulphated glycosaminoglycans (GAGs) rose during the second decade; the highest increases were in dermatan and chondroitin sulphates. The content of arterial EC showed significant positive correlations with those of GAGs, but associations with the contents of DNA, total protein, and collagen were not significant. As judged by the observed gradual increase in arterial EC and a change in its fatty acid composition, there is a continuous increase with age in LDL-derived EC in the arterial wall. The mechanism of this accumulation is unknown, but the findings provide circumstantial evidence to support the concept that arterial GAGs may cause retention of plasma-derived lipids, which may subsequently be altered and internalized by the intimal cells.

The effects of post-mortem autolysis on the biochemical composition of coronary intima-medias were studied by keeping the coronary arteries of 25 slaughterhouse pigs at +4 degrees C for periods up to 7 days. The samples were analysed for DNA, total protein, collagen, glycosaminoglycans (GAGs), free and esterified cholesterol, triglycerides, phospholipid fractions, and fatty acid composition in various lipid classes. The content of sulphated GAGs decreased steadily, whereas that of hyaluronic acid remained unchanged. These alterations led to a significant decrease in the content of total GAGs and to an increase in the percentage of hyaluronic acid in total GAGs. The results indicate a continuous post-mortem degradation of arterial proteoglycans. After 7 days storage, there was a significant increase in the content of free fatty acids, and the composition of this fraction was changed by increases in the relative amounts of oleic and linoleic acids. These changes were accompanied by an increase in lysolecithin and a decrease in lecithin, which suggests a post-mortem action of arterial phospholipases.

Men in Eastern Finland show a substantially higher rate of coronary heart disease (CHD) than men in the Western part of the country. To study possible differences in the biochemical composition and atherosclerotic involvement of coronary arteries between these two populations, we analyzed major lipid and non-lipid components of coronary arteries from 15- to 60-year-old Finnish men after accidental death. The material consisted of 59 age-matched pairs from East and West Finland, respectively, collected at successive autopsies during 1979-1983. The coronary arteries from East Finland contained significantly more esterified cholesterol and a higher percentage of oleate in cholesteryl esters. The findings were most conspicuous under the age of 40 years, and imply a higher degree of atherosclerosis together with an increased rate of intracellular cholesterol esterification in coronary arteries in Eastern as compared with Western Finland. The vessels from East Finland also tended to contain more free cholesterol and raised lesions, but the differences were not statistically significant. No major regional differences were seen in total phospholipids, phospholipid subfractions, DNA, calcium, collagen, total protein, or glycosaminoglycans.

Necropsy findings in patients with Down's syndrome have suggested an absence of atherosclerosis throughout the cardiovascular system, but there are also contradictory results. We compared the left coronary arteries of 15 institutionalised Down's syndrome patients (5 males, 10 females, mean age 51 years) with those of 6 other institutionalised mentally retarded patients (4 males, 2 females, mean age 49) and 20 normal, free-living subjects (10 males, 10 females, mean age 48) by macroscopic inspection of the opened coronary arteries and by biochemical analysis of their intima-media. The arteries of Down patients contained a lower percentage of raised lesions and less calcium than the arteries of the control groups. Thus, even though the coronary arteries of mongoloids were not completely free of atherosclerosis, it was milder than in other mental patients and free-living subjects of the same age.

Intimal thickenings of the coronary arteries were found in healthy children who died violently, of both sexes even in children under 5 years of age. The average incidence was 53 % of the 75 cases. Splitting of the internal elastic lamina was the primary finding, followed by local increase in smooth muscle cells. The thickening could occupy 50 % of the coronary lumen. The accumulation of esterified cholesterol in the coronary arteries began before the age of 10 years. The fatty acid composition of the cholesterol esters suggests that they are derived from the blood. The question whether the thickenings are precursors of forthcoming coronary atheromas needs further detailed studies, especially in young adults.