The umbilical artery was chosen as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. Pronounced intimal changes were seen in the arteries from smoking mothers; the most important findings were degenerative changes of the endothelium such as swelling, blebbing, contraction, and subsequent opening of the endothelial junctions with formation of subendothelial edema. Other observations included dilation of the endoplasmic reticulum in the endothelium and reparative changes such as a considerable widening of the basement membrane. Since similar changes can be induced in arteries of animals by exposure to carbon monoxide or perfusion with nicotine, we conclude that the present study supports the concept that tobacco smoking is harmful to the vascular endothelium. This study also contributes to an understanding of the mechanism through which vascular injury is provoked in heavy smokers. KEY WORDSpregnancy placenta carbon monoxide nicotine tissue hypoxia vascular injury• Clearly, a close connection exists between tobacco smoking and development of arterial diseases, especially coronary heart disease and peripheral arterial disease (1). The question is how does tobacco smoke provoke arterial damage. Evidence accumulated during the last decade indicates that the carbon monoxide in tobacco smoke is harmful to the arterial wall (2). Exposure to low doses of carbon monoxide accelerates atherogenesis in cholesterol-fed animals (3-5) and produces significant ultrastructural changes in the aortic and the coronary endothelium of rabbits and primates that are indistinguishable from early atherosclerosis (6, 7). For obvious reasons similar exposure studies and subsequent vascular biopsies cannot be performed in humans. Moreover, a comparison of vascular biopsy studies in human smokers and nonsmokers has not been published to date. As a possible model for evaluating the vascular damage provoked by tobacco smoking in humans, the umbilical artery of babies of smoking and nonsmoking mothers was used for ultrastructural studies in the present paper. Methods PATIENTSPregnant women admitted to the Department of Obstetrics and Gynecology at Rigshospitalet were selected for the study. All patients were examined by the same investigator, and each subject completed a questionnaire on smoking habits before and during pregnancy. Twenty-eight patients took part in the study, 13 smokers and 15 nonsmokers. All smokers were inhaling cigarette smokers. One subject smoked 40-60 cigarettes daily.Women suffering from hypertension, diabetes, and other diseases and those with Rh negative blood types were not used in this study. The patients chosen for the study were normal before and during the pregnancy: all laboratory investigations (hemoglobin, blood, sugar, etc.) including urinary analyses for sugar, protein, and estriol were normal. Therefore, the only ...

In cholesterol-fed rabbits, alloxan-dlabetes has an antt-atherogenlc effect, which is associated with severe elevation of plasma triglyceride concentrations. To study this effect, we measured llpoprotein sizes and aortic permeability coefficients for chotesteryl ester and for albumin In hypertriglycerldemlc diabetic cholesterol-fed rabbits and In normotriglyceridemlc cholesterol-fed rabbits. With the same high cholesterol concentration in plasma, hypertrlglyceridemlc diabetic rabbits had 70% of plasma cholesterol In very large llpoprotelns (diameter >75 nm), whereas normotrlglycerldemlc rabbits had only about 10% of plasma cholesterol in these giant llpoprotelns. The aortic permeability coefficients for cholesteryl ester In hypertriglycerldemlc diabetic cholesterol-fed rabbits was only 10% to 50% of that In normotriglyceridemlc cholesterol-fed rabbits. Aortic permeability coefficients for albumin did not differ significantly between the hypertrlglyceridemlc and normotriglyceridemlc rabbits. The results suggest that the large size of a major fraction of plasma llpoprotelns in the hypertrlglyceridemlc diabetic cholesterol-fed rabbits Is responsible for the relatively low aortic permeability coefficient for cholesteryl ester from plasma and hence for reduced atherogenesis In these animals. (Arteriosclerosis 8:421-428, July/August 1988) I t Is generally recognized that humans with diabetes mellitus have more atherosclerosis than do nondiabetic humans. This seems to conflict with the finding that the induction of alloxan-diabetes has an anti-atherogenic effect in cholesterol-fed rabbits.1 -8 The antj-atherogenic effect is not caused by the alloxan injection, per se, 1 or by the effect of alloxan on tissues other than the pancreas. 5Treatment of these animals with insulin reverses the anti-atherogenic effect.0 Altoxan-dlabetic rabbits that are protected against atherosclerosis have a parallel rise in plasma cholesterol, lipid phosphorus, and neutral fat. 3The major part of this elevated plasma cholesterol is carried in the triglyceride-rtch, large, less-dense lipoproteins. 489 When plasma triglycerides are increased only slightly in the alloxan-diabetic rabbit, no antiatherogenic effect is seen. 10Duff and Payne 3 suggested that elevated plasma lipid phosphorus stabilizes cholesterol in plasma and thereby prevents deposition of cholesterol in the arterial wall of the alloxan-diabetic rabbit. They also postulated that high levels of plasma neutral fat may play some part. Recently, Brecher et al. 8 have shown that the d<1.019 g/ml lipo- A preliminary report was given at the American Heart Association's 59th Scientific Sessions, Dallas, Texas, November 1986. Received September 17,1987 revision accepted March 9,1988. protein fraction from diabetic cholesterol-fed rabbits, in contrast to beta very low density lipoprotein (0-VLDL) from nondiabetic cholesterol-fed rabbits, did not stimulate cholesteryl ester formation in mouse peritoneal macrcphages. They suggested that diabetic lipoproteins do not exhibit the appropria...

The aim of this study was to investigate the possibility that the permeability characteristics of the arterial wall are related to the development of atherosclerosis. The in vivo regional variation of aortic permeability to iodinated human low density lipoprotein (LDL) in normal rabbits was compared with the regional variation in aortic cholesterol accumulation in cholesterol-fed rabbits. Aortas were divided into the aortic arch, thoracic aorta, and abdominal aorta, and each of these three parts was further subdivided into four segments of similar size. The permeability to LDL was 40±7 nl • cm" 2 • hr" 1 (mean±SEM, n=ll) in the most proximal segment of the aortic arch and decreased throughout the length of the aorta to 3±1 nl • cm" 2 • hr" 1 in the most caudal segment of the abdominal aorta. In such normal rabbits the aortic cholesterol content was similar in all 12 arterial segments at 0.08 ±0.005 /unol/cm 1 (mean±SEM, n=3xL2). Aortic cholesterol accumulation was determined in other rabbits with an average plasma cholesterol level of 32±1 mmol/l for 96 days; the cholesterol content in the most proximal segment of the aortic arch was 2.7±0.5 fimo\/cm 2 (mean±SEM, n = ll) and decreased with increasing distance from the heart to 0.17±0.03 fisnol/cm 1 in the most caudal segment of the abdominal aorta. Linear regression analysis showed a close positive association between the permeability to LDL of a given aortic segment and the cholesterol accumulation in that same aortic segment after cholesterol feeding (r 2 =0.96, p<0.001). These results suggest that the aortic permeability to LDL is an important predictor for the development of atherosclerosis in cholesterol-fed rabbits. (Arteriosclerosis and Thrombosis 1992;12:1402-1409 KEY WORDS • aortic permeability • atherosclerosis • cholesterol-fed rabbits • LDLs I t is well established that atherosclerotic lesions are characterized by cholesterol accumulation, an increase in intercellular matrix, and cell proliferation. Several lines of evidence from both rabbit and human studies support the conclusion that the cholesterol in atherosclerotic lesions is derived from plasma hpoproteins.1 " 5 In humans as well as rabbits, there is considerable variation in the extent and severity of atherosclerotic lesions between different arterial sites, even though all arterial surfaces within a given individual or rabbit have been exposed to the same plasma cholesterol level.6 -9 This suggests that regional variation in lipoprotein-arterial wall interactions is important for the development of atherosclerosis. Such differences between lesion-resistant and lesion-prone arterial sites could be caused by differences in arterial lipoprotein influx, retention, degradation, or efflux. Differences in arterial lipoprotein influx between arterial sites would be reflected in differences in aortic permeability between these sites. The present study considers the hypothesis that the aortic permeability to human low density lipoprotein (LDL) is a predictor of aortic cholesterol accumulation in chole...