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Seasonal variations in the biophysical properties of rabbit aorta and its susceptibility to arteriosclerosis.

The physiological variations in the mechanical properties of rabbit aortae in relation to the periods of hair shedding were studied. The load-strain curves of the eight proximal thoracic segment in 15 shedding and 15 non-shedding male albino rabbits were analysed. The slope of the curves (tangent of the angle between the linear region of the load-strain curve and the strain axis) was decreased in the shedding animals compared to that of the non-shedding animals and the toe of the load-strain curves was significantly lower towards the x-axis in the shedding animals. The observations indicate a lower stiffness, that is increased elasticity, of the aortae of rabbits during hair shedding. The increased elasticity during hair shedding may explain the previously reported resistance to experimental arteriosclerosis caused by the hemodynamic strain elicited by exposure to systemic hypoxia. A decrease in the aortic content of collagen and of sulfated glycosaminoglycans, and an increase in the content of hyaluronic acid, may be of importance in the alterations of the mechanical properties of rabbit aorta during hair shedding.

Animals↗

Plethysmographic pulse wave amplitude and future leg arteriosclerosis.

A low pulse wave amplitude during calf plethysmography at 55 years of age was previously found to be associated with an increased mortality and incidence of myocardial infarction. In order to test the hypothesis that a low pulse wave amplitude is associated with an increased risk of future leg atherosclerosis as well, we have studied the relationship between a low ankle-brachial pressure index (ABPI; < 0.9) at 68 years of age and the pulse wave amplitude at 55 years of age in that same cohort. The prevalence of a low pulse wave amplitude (< or = 5 mm; lowest quintile) among men with a low ABPI (42%) was more than twice as high as it was among men who had a normal ABPI (19%) (P < 0.001). No association was found between a low ABPI and the plethysmographically recorded leg blood flow at 55 years of age. A low pulse wave amplitude might reflect early symptom-free arteriosclerosis, or age-dependent non-arteriosclerotic loss of vessel wall elasticity. The relationship between a low pulse wave amplitude and a low ABPI remained when controlling for smoking, hypertension and hyperlipidaemia. It is concluded that pulse wave measurement by plethysmography contributes information to improve leg atherosclerotic risk assessment in individuals exposed to known risk factors.

Aged↗

Experimental arteriosclerosis treated by conventional and laser endarterectomy.

Open laser endarterectomy was compared to standard surgical endarterectomy in the rabbit arteriosclerosis model. The aorta was exposed by a thoracoabdominal exploration in 16 rabbits. In Group I (8 rabbits), a conventional endarterectomy (CE) was performed with standard vascular instruments. In Group II (8 rabbits), laser endarterectomy (LE) was performed with an argon ion laser (488 nm and 514.5 nm) at a power of 1.0 W. Aortas were fixed, serially sectioned (6 micron) and stained (H +/- E) following each procedure. Gross and light microscopic examination revealed identical results for the endarterectomy surfaces of CE and LE. The proper cleavage plane within the media was developed with both techniques and the remaining arterial wall was not damaged with either procedure. The end points of LE were consistently superior to those of CE because of phototherapy fusion. The LE end points were tapered and the intima was fused. Intimal flaps were seen in 2/8 CE experiments and the remaining end points exhibited an uneven transition. LE required an average energy density of 124 +/- 9 J/cm2. We conclude that LE provides a satisfactory method for the in vivo evaluation of laser radiation upon arteriosclerotic arteries. LE may be the way to begin clinical laser trials.

Animals↗

Lack of effect of ischemia and dipyridamole on prostacyclin production in arteriosclerosis obliterans.

Six patients with advanced arteriosclerosis obliterans in the lower extremities were subjected to an exercise test on a tread mill with and without dipyridamole treatment. Prostacyclin (PGI2) release was measured by the concentration of its stable metabolite, 6-keto-prostaglandin F1 alpha in plasma. All the patients suffered from ischemic pain during both tests, but no changes were seen in plasma 6-keto-PGF1 alpha. Dipyridamole did not affect the physical performance. Our results suggest that atherosclerotic vessels do not increase PGI2 production in response to ischemia and that a single dose of dipyridamole does not change PGI2 production.

6-Ketoprostaglandin F1 alpha↗

Non-invasively detected carotid stenosis and ischaemic heart disease in men with leg arteriosclerosis.

Since the excess mortality rate associated with an ankle-brachial blood-pressure index (ABPI) less than 0.9 was only partly explained by an excess cardiovascular mortality, we believe that leg artery disease should not only be regarded as a marker of generalised arteriosclerosis but also as a sign associated with an increased risk of premature death. 439 men who were part of a prospective population study in Malmö, Sweden, were, at 68 years of age, invited to a health examination including, ABPI, carotid-artery ultrasonography, and 24 h ambulatory electrocardiographic monitoring. Cause-specific mortality and incidence of myocardial infarction (MI) during 8 years of follow-up was compared in men with and without signs of arteriosclerotic disease. Of 60 men with an ABPI < 0.9, 20 (33%) had angina pectoris or previous MI. Another 11 (18%) had silent ST-segment depression (> or = 1 mm); 3 (5%) had a history of stroke; and 17 (28%) had symptom-free carotid stenosis (> 30% reduction of the cross-sectional diameter). Total mortality rate in men with no signs of arteriosclerotic disease was 19.6 per 1000 person-years and cardiac event rate (fatal and non-fatal MI and death from chronic ischaemic heart disease was 8.6 per 1000 person-years). Leg artery disease, carotid stenosis, and ischaemic heart disease were in a univariate analysis all associated with an increased cardiac event rate and an increased total mortality rate. In a multivariate analysis an ABPI less than 0.9 was associated with a 2.4 times higher total mortality (95% CI 1.5-3.9) and a 2.0 times higher cardiac event rate (1.1-3.9). Carotid stenosis and ischaemic heart disease contributed to the risk for MI (RR 2.1; 95% CI 1.2-3.8; and 2.1; 1.2-3.9, respectively), whereas no independent association with total mortality was found.

Aged↗

Perioperative changes in coagulative and fibrinolytic function during surgical treatment of abdominal aortic aneurysm and arteriosclerosis obliterans.

To determine the factors which influence perioperative coagulative and fibrinolytic function, we studied 41 patients who underwent surgical repair of unruptured abdominal aortic aneurysm (AAA) and 30 patients who underwent arterial reconstruction for arteriosclerosis obliterans (ASO). In patients with AAA, the levels of fibrin/fibrinogen degradation products (FDP) (11.4 +/- 20.1 micrograms/ml), thrombin-antithrombin III complex (TAT) (22.0 +/- 21.8 micrograms/l), plasmin-alpha 2 plasmin inhibitor complex (PIC) (2.6 +/- 2.9 micrograms/ml) and d-dimer of cross-linked fibrin degradation products (D-D) (8.4 +/- 10.8 micrograms/ml) were elevated, particularly when the AAAs had a large mural thrombus surface area or were accompanied by aneurysm of the iliac or femoral artery. In arterial aneurysms, blood coagulability and secondary fibrinolytic activity were believed to be enhanced. In patients with ASO, the level of TAT (17.2 +/- 24.8 micrograms/l) was so elevated that they were considered to show chronic hypercoagulability. Among the ASO patients with aorto-iliac lesions, those with concomitant graft occlusion or anastomotic aneurysm had significantly elevated levels of TAT. Proximal arterial occlusion or accompanying aneurysm in the ASO patients was associated with increased levels of PIC and D-D. Postoperative fluctuations in conventional hematological variables did not differ significantly among the surgical procedures. Conventional markers showed a transient decrease due to consumption during surgery, and a subsequent recovery or an actual increase within several days after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The mechanism of intimal thickening in arteriosclerosis.

The limitations of current theories of the mechanism of intimal thickening in arteriosclerosis are briefly reviewed. The suggestion is advanced that this change is due to intimal oedema, arising from failure of the lymphatic system of the surrounding tissue to remove adequately, protein-containing fluid filtering outwards through the vascular endothelium. It is postulated that such local environmental influences account for the variability in the degree of arterial degeneration seen in different arteries, and in different portions of the same artery.

Arteries↗

The effect of aging and arteriosclerosis on human skin blood flow.

Skin blood flow in the deltoid region of 65 men was measured by the xenon 133 clearance method and in studying the correlation of age, total cholesterol and systolic blood pressure to skin blood flow, the following results were obtained. (1) Skin blood flow significantly decreased with increase in age. In calculating skin blood flow at 20 and 70 years of age from the regression line between skin blood flow and age, it was estimated that skin blood flow at 70 years of age decreased to 40% of that at 20 years of age. (2) Skin blood flow significantly decreased with increase in total cholesterol and systolic blood pressure. (3) Skin blood flow showed the closest correlation with age, followed by total cholesterol and systolic blood pressure which showed a weak correlation. It is estimated from the foregoing results that as skin blood flow in patients with arteriosclerosis decreases more in elderly individuals than in young persons, their wound healing is delayed.

Adult↗

Influence of high density lipoprotein (HDL), prepared from human blood, on prostanoid formation, serum and tissue lipids and development of arteriosclerosis in cholesterol rich fed rabbits.

The i.v. administration of high density lipoprotein (HDL) into cholesterol fed rabbits decreased statistically significantly the serum level of total cholesterol and of low density lipoprotein cholesterol after a feeding period of 8 weeks. These diminished levels of cholesterol were associated with a statistically significant reduction in the levels of cholesterol esters in kidneys and platelets but not in hepatic tissue or in aorta. Macroscopically detectable arteriosclerosis was not statistically significantly diminished. The formation of prostanoids by the aorta remained unchanged. The atherogenic role of immunologic factors acting against the heterologous HDL may have compensated for the antiatherogenic HDL action on plasma and tissue lipids.

Animals↗

Increased calcium and decreased magnesium concentrations and an increased calcium/magnesium ratio in spontaneously hypertensive rats versus Wistar-Kyoto rats: relation to arteriosclerosis.

Alterations in the metabolism of calcium and magnesium have been implicated in the pathogenesis of primary hypertension. Calcium influx across the external cellular membrane in smooth muscle cells and cardiomyocytes plays a crucial role in the control of cellular excitation contraction and impulse propagation. Intracellular calcium and magnesium concentrations are controlled by reversible binding to specific calcium-binding proteins. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium channels, and binding to the membrane. In cell membranes and in lymphocytes of essential hypertensives our group showed increased calcium and a decreased magnesium and increased calcium/magnesium ratio in hypertensive cells. In this context, in aortic smooth muscle cells from 13 spontaneously hypertensive rats (SHR) of the Münster strain (systolic blood pressure 188.4 +/- 9.8 mm Hg) and 13 normotensive rats (NT, systolic blood pressure 118.5 +/- 7.2 mm Hg) aged 9 months, the intracellular calcium and magnesium contents were measured under nearly in vivo conditions by electron probe microanalysis. Measurements were performed in aortic cryosections 3 microm thick; the calcium content was 124.7 +/- 4.5 mmol/kg dry weight in SHR versus 110.3 +/- 4.1 mmol/kg dry weight in NT (mean +/- SD, P <.01 for both), the magnesium content was 35.5 +/- 3.9 in SHR versus 50.1 +/- 4.9 mmol/kg dry weight in NT (P <.01 for both). The calcium/magnesium ratio was significantly increased in SHR versus NT (3.56 +/- 3.9 versus 2.23 +/- 0.27 [P <.01 for both]). Thus, aortic smooth muscle cells from SHR are characterized by a markedly elevated intracellular calcium and decreased intracellular magnesium contents compared with normotensive cells. Cellular calcium and magnesium handling is disturbed in SHR aortic smooth muscle cells as it is in hypertensive blood cells. The increased calcium/magnesium ratio in hypertensive cells is a pathogenetic factor for the development of arteriosclerosis and hypertension.

Animals↗

Association between white blood cell count and carotid arteriosclerosis in Japanese smokers.

Recent studies have shown the relationship between general inflammatory markers and ischemic heart and cerebrovascular diseases. Here we have investigated the potential association between the circulating white blood cell count and carotid arteriosclerosis in apparently healthy individuals. Between 1994 and 1998, 3455 subjects who had undergone general health screening tests including carotid ultrasonography were enrolled in this study. The intertertile cutoff points for the white blood cell count were 5.1 x 10(3) and 6.4 x 10(3) microL(-1) in the male subjects and 4.6 x 10(3) and microL(-1) in the female subjects. The prevalence of carotid plaque in the first (lowest), the second, and the third tertiles was 19, 28, and 28% in the male subjects, respectively (P < 0.0001), and 10, 15, and 14% in the female subjects, respectively (n.s.). The multivariate analysis showed that the male subjects in the second and third tertiles had increased risk for carotid plaque with odds ratios of 1.54 (95% CI 1.18-2.01) and 1.47 (95% CI 1.11-1.95), respectively, compared to those in the first tertile. When male subjects were subdivided according to their smoking status, the association between white blood cell count and carotid plaque was significant in those who smoked, but not in those who had never smoked. These data suggested the possible association between the circulating white blood cell count and formation of carotid plaque in male smokers, but not in male never smokers or in females, in an apparently healthy Japanese population.

Arteriosclerosis↗

Prevalence of asymptomatic arteriosclerosis obliterans and its relationship with risk factors in inhabitants of rural communities in Japan: Tanno-Sobetsu study.

OBJECTIVES: Since arteriosclerosis obliterance in the legs (ASO) causes deterioration of the prognosis of the elderly, prevention of ASO is important for maintenance of their quality of lives. We studied the prevalences of ASO in rural communities in Japan. METHODS AND RESULTS: We measured the ratio of systolic blood pressure in the leg to that in the arm (ABI) using a new device, Form PWV/ABI, in 1398 subjects of both sexes. Subjects with ABI values below 0.9 were considered to have ASO. The prevalence of ASO was 2.7% in all of the subjects, 1.0% in subjects under the age of 60 years, and 3.4% in subjects aged 65 years or more. Multiple regression analysis showed that ABI was correlated with plasma level of total cholesterol in men. There were no significant differences of the mean age, mean fasting plasma glucose level and percentage of patients who smoked between the ASO group and non-ASO group in each sex. Mean cholesterol level in our subjects is lower than the reported levels in Europeans and Americans. The prevalence of ASO increased with increase in the number of risk factors in individual subjects. CONCLUSIONS: Among the atherosclerotic risk factors, age and total cholesterol seem to be more important risk factors of ASO than others.

Adult↗

Effects of selective LDL apheresis on plasma concentrations of ICAM-1, VCAM-1 and P-selectin in diabetic patients with arteriosclerosis obliterans and receiving maintenance hemodialysis.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a serious complication in patients with end-stage renal disease (ESRD) caused by diabetic nephropathy. Adsorption of low-density lipoprotein (LDL) has been performed to treat ASO. While efficacy of this treatment has been reported in limb ischemia, the mechanism underlying the benefit remains unclear. We investigated how LDL adsorption affected soluble adhesion molecules; P-selectin, an endothelial and platelet activation marker; inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tissue necrosis factor (TNF)-alpha; and lipids in serum. METHODS: Selective LDL adsorption by dextran sulfate columns (LDL apheresis) was performed weekly for 10 weeks to treat eight hemodialysis patients with ASO, ESRD, and type 2 diabetes mellitus. Serum was sampled before and immediately after apheresis. RESULTS: LDL apheresis was performed safely. After LDL apheresis lipid concentrations were significantly reduced and clinical findings, such as Fontaine's classification and ankle brachial pressure index values, were improved. Pretreatment concentrations of soluble intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1) and also P-selectin were higher in patients than healthy controls. After apheresis these decreased, especially P-selectin. IL-1beta, IL-6, and TNF-alpha concentrations before apheresis were similar to those in controls and were unaffected by treatment. CONCLUSION: Effectiveness of LDL apheresis against ASO may involve decreased endothelial cell and platelet activation.

Aged↗

Close association of hypoadiponectinemia with arteriosclerosis obliterans and ischemic heart disease.

Adiponectin is an adipose-derived cytokine, and it is suggested that hypoadiponectinemia increases the prevalence of ischemic heart disease (IHD). The present study was undertaken to determine serum adiponectin levels in patients with arteriosclerosis obliterans (ASO) and IHD. Forty-nine patients with ASO and 49 age-, sex-, and body mass index-matched control subjects were examined. The diagnosis of ASO was derived from an ankle brachial index of less than 0.90 and stenotic or obstructive change in angiogram. Ischemic heart disease was diagnosed by ischemic or stenotic change in ECG, treadmill, or coronary angiogram. Serum adiponectin level was 8.6 +/- 0.9 microg/mL in the patients with ASO, a value significantly less than that of 12.4 +/- 1.0 microg/mL in the control subjects ( P < .01). Next, we subgrouped the subjects into 4 groups according to the presence of ASO and IHD. Serum adiponectin levels were 9.4 +/- 1.5 and 10.2 +/- 1.6 microg/mL in the subjects with ASO (n =23) and those with IHD (n = 13), respectively. It was further reduced to 7.9 +/- 1.2 microg/mL in the subjects having both ASO and IHD (n = 26), a value significantly less than that of 13.2 +/- 1.4 microg/mL in the control subjects (n = 36; P < .05). Serum high-density lipoprotein cholesterol was significantly less in the subjects with ASO than in the control subjects (42.1 +/- 1.7 vs 48.5 +/- 2.0 mg/dL; P < .05), but there were no differences in blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, and uric acid levels. The present results indicate that a reduction in serum adiponectin level is associated with the prevalence and magnitude of systemic atherosclerosis including IHD and ASO.

Adiponectin↗

Relations between spontaneous and induced arterial lesions in swine and arteriosclerosis in humans.

The rabbit which for practical reasons is so frequently used for experimental arteriosclerosis considerably differs from humans in its metabolism, nourishment, and arterial wall responses to atherogenic noxae. In this respect, domestic pigs show more resemblance to the conditions in man, and they have recently been used for experimental research work in the field of atherosclerosis. Our own investigations performed with a view to constructing an antherosclerosis model being as far as possible resemblant to conditions prevailing in humans have shown that among various forms of diets only one combined form which is rich in cholesterol (1.5 percent) and lipids (15 percent) produces changes in the intima that in certain arterial regions correspond to lesions found in humans. These are lipofibrous beds up to complicated atheromas. The location of the spontaneous changes (without atherogenic diet) suggest that these may be considered as early stages. The various forms of development were studied light- and electron-microscopically; moreover the development of the blood lipids was determined biochemically during the experiment.

Animals↗

Protective effect of dietary monounsaturated fat on arteriosclerosis: beyond cholesterol.

The consumption of diets enriched in monounsaturated fat has been related to a lower rate of coronary heart disease. It is well known that this dietary model decreases LDL-cholesterol plasma levels when replacing a saturated fat enriched diet. For this reason, a high monounsaturated fat diet is now being advocated to prevent cardiovascular disease, especially in Mediterranean countries. However, some expert panels-the Joint Task Force of European and other Societies on Coronary Prevention and the International Task Force for Prevention of Coronary Heart Disease-recommend replacing dietary saturated fat by complex carbohydrates, limiting the intake of total fat to <30% of the energy and monounsaturated fat to no more than 10-15% of total calories, reaching a similar effect on LDL-cholesterol plasma levels to a high monounsaturated fat diet. The most appropriate nutritional model to prevent arteriosclerosis should be supported by research into other biological effects of both diets. Therefore, it is interesting to review the non-lipid effect of monounsaturated fat, starting with its influence on other cardiovascular risk factors, such as carbohydrate metabolism and blood pressure. Moreover, substantial evidence of the effect of dietary monounsaturated fat on a wide range of healthy benefits beyond cholesterol, which have been investigated in recent years, such as lipoprotein oxidation, coagulation, fibrinolysis and endothelium, will be discussed. Furthermore, many observational epidemiological studies suggest that a high intake of monounsaturated fat is associated with reduced coronary risk and this will be analyzed in accordance with the clinical evidence to discuss the best dietary model to prevent coronary artery disease.

Arteriosclerosis↗

Spontaneous arteriosclerosis in old, male, virgin Sprague--Dawley rats.

Virgin, male, Sprague--Dawley rats were observed from 3 to 34 months of age. Systolic blood pressure rose progressively with age, reaching abnormally elevated levels in some, becoming abnormally low in others. The old virgin males gained and then lost weight progressively with age, their pituitary and adrenal glands were heavier than young rats, and their thymi were greatly involuted. The old virgin rats manifested fatty infiltration of the liver and islet beta cell degranulation concomitant with hyperlipidemia, hyperglycemia, and elevated circulating corticosterone levels. Spontaneous arteriosclerosis, identical to that found in younger breeder rats was found in these old virgin males. Therefore, the vascular and other degenerative changes found in young breeder rats in considered to be an example of accelerated arterial disease.

Aging↗

Influence of vein valves in the development of arteriosclerosis in venoarterial grafts in the rabbit.

Coronary saphenous vein grafts in human beings have a more limited long-term patency rate than internal thoracic artery grafts, primarily because of more rapid development of arteriosclerosis. The factors responsible for this increased susceptibility are not completely understood. To test the hypothesis that vein valves may influence this process, we studied 48 hypercholesterolemic rabbits with jugular vein grafts interposed into the carotid arterial circulation. In 24 animals (group A), the vein segments did not contain a vein valve. In the other 24 animals (group B), a vein valve was present. Both groups were further divided in four subgroups of six to be put to death at 2, 4, 6, and 8 weeks after the operation. All animals were fed a 2% cholesterol diet. At postmortem examination, alternate 2 mm sections were either stained with hematoxylin and eosin for histologic and morphometric studies or frozen in liquid nitrogen for immunohistochemistry and in situ hybridization studies. Proliferating cell nuclear antigen immunostaining was used to study cell proliferation. Wall thickness of vein grafts increased with time. During the first 2 weeks intimal and medial thickening was primarily due to an increase in numbers of cells. Between 2 and 6 weeks further intimal and medial thickening occurred, but without additional increase in cell numbers. After 6 weeks, foam cells and lipid deposits started to appear. By 8 weeks, changes identical to those seen in arteriosclerotic plaques in human beings were evident. These changes developed sooner and with more intensity in group B animals (p < 0.01 to 0.001), and they developed faster and with more severity in segments of vein located distal to the valve than in the segments located proximal to the valve (p < 0.001). This is the first controlled experiment demonstrating that the presence of valves in the vein segments is associated with augmented and accelerated intimal changes leading to vein atheromatosis.

Animals↗