Disease patterns at arterial branches and their relation to flow

The distribution of lesions around arterial branch points is complex and changes with age. Four distinct patterns - here termed the arrowhead pattern, the lateral pattern, the upstream streak and the volcano - have been reported around the origins of intercostal arteries in the human aorta at different ages. The first two patterns also occur in young and old rabbits, the third in minipigs, and the fourth in apolipoprotein E/LDL receptor knockout mice. It is unclear how all four patterns can depend solely on flow; a particular problem is that the prevalence of lipid deposition remains highly nonuniform for several branch diameters upstream of the ostium. Variations in the prevalence of fatty streaks may originate near the branch and then spread by the migration of activated endothelial cells towards the heart. The pattern of raised lesions may reflect a different aetiology.     

Numbers of cells and cell proliferation in intima of different human arteries

Increased cell proliferation in early atherosclerotic lesions is recognized as an essential event of atherogenesis but the levels of cell proliferation in different stages of atherosclerotic plague formation in different types of human large arteries are still insufficiently studied. In the present work, we studied intima thickness and proliferation of newly "infiltrates" hematogenous and resident cells in atherosclerotic lesions of the carotid and coronary arteries and compared these parameters with those in the aorta, reported by us in earlier publication. Analysis of intima thickness and proliferation in grossly unaffected intima and in different types pf atherosclerotic lesions (initial lesions, fatty streaks, lipofibrous, plaques, and fibrous plaque) revealed that although there were similar tendencies in the change of the infiltration levels of hematogenous cells and proliferation in different types of arteries, there were significant quantitative differences between different types of arteries. Hematogenous cells in lipofibrous plaques of the coronary and carotid arteries were found to account for a third and almost for a half of the total cell population, respectively, while atherosclerotic lesions in the aorta, as it has been shown by us earlier, to contain no more than 15% ofhematogenous cells. This suggests that the contribution of hematogenous cells to the development of atherosclerosis in the carotid and the coronary artery appears to be more significant than that in the aorta. Despite the differences in numbers of accumulating hematogenous cells in the intima, a similar "bell-shaped" dependence of cell numbers on the lesion type, involved in the following sequence: unaffected intima-initial lesions-fatty streaks-lipofibrous plaques-fibrous plaques, was detected in the coronary and carotid arteries. The visualization of proliferating cells (PCNA-positive) in atherosclerotic and unaffected zones of the coronary and carotid arteries revealed similar patterns. The maximum numbers of PCNA-positive resident cells were identified in lipofibrous plaques. The changes in the total cell numbers were accompanied by the changes in the numbers of both proliferating resident cells and proliferating hematogenous cells.     

Spontaneous Aortic Lesions in Roe Deer (Capreolus Capreolus L)

In 34 out of 60 aortas from roe deer, aged from 6 months to more than 8 years, aortic lesions were found. The frequency of affected regions involved were, in the posterior abdominal portion 53.3 %, in the aortic arch 18.3 %, in the anterior abdominal portion 16.7 %, in the posterior thoracic portion 8.33 % and in the anterior thoracic portion 3.3 %. Of the observed lesions, fatty streaks were seen in 3, fatty streaks and fibrous plaques in 3, fatty streaks with complicated lesions (calcification and acid mucopolysaccharides) in 14 and fibrous plaques with complicated lesions in 14 of the aortas. Elastic tissue degeneration of the inner two thirds of the tunica media was principally found in the aorta of the animals beyond 4 years of age. The lesions significantly (P < 0.001) increased in number and severity with age and appeared to be more progressive in pregnant animals. There was, however, no significant difference between affected male and female animals in the different age groups.     

Participation of smooth muscle cells in the formation of atherosclerotic plaques]

A study of the participation of the smooth muscle cells in the formation of atherosclerotic lesions was made on the autopsy material with the use of specific antiserum to the smooth muscle actomyosin and of indirect Coons' method. Typical forms of atherosclerotic lesions in the aorta, cerebral vessels and coronary arteries were studied. Smooth muscle cells were detected in the thickened intima alongside the atherosclerotic lesions, in fatty streaks, in the fibrous tissue of the atherosclerotic plaque, but they were not found in the atheromatous masses. The proliferation and migration of the smooth muscle cells is regarded as an essential factor in the pathogenetic mechanisms of atherosclersis.     

Spontaneous Aortic Lesions in Moose (Alces Alces L)

In 17 out of 22 aortas from moose, 6 months to more than 18 years, aortic lesions were found. Five different types of lesions were observed, fatty streaks were seen in 1, fibrous plaques in 7, fatty streaks with complicated lesions (calcification and acid mucopolysaccharides) in 3, fibrous plaques with complicated lesions in 2 and fibrous plaques with complicated lesions and fat droplets in 4 of the aortas. Elastic tissue degeneration of the inner two thirds of the tunica media was principally found in the aorta of the animals beyond 4 year of age. There was no statistical evidence for a correlation between age and frequency but a trend towards age dependence was seen. The percentage of involved surface was found to increase significantly (0.05 > P > 0.02) with age. There was no significant difference between affected male and female animals in the different age groups. The frequency of involved surface in different affected regions, comprising all age groups were, in the posterior abdominal portion, 13.0 %, in the anterior abdominal portion, 3.0 %, in the posterior thoracic portion 5.2 %, in the anterior thoracic portion, 0.1 % and in the aortic arch, 0.1 %. Proliferating endothelial cells and the source of smooth muscle cells were discussed.     

心电图ST段不同改变与急性心肌梗死患者冠脉造影病变特点及生活质量的相关性研究

目的:探讨心电图ST段不同改变与急性心肌梗死患者冠脉造影病变特点及生活质量的相关性。方法:选取选取2015年6月到2017年6月在本院接受治疗的急性心肌梗死患者208例,根据心电图ST段的改变情况将患者分为ST段抬高组(124例)、ST段压低组(64例)、ST段无偏移组(20例),所有患者进行冠脉造影检查和常规治疗,比较治疗前三组患者的冠脉造影情况和冠脉狭窄程度,比较治疗1个月后三组患者的生活质量评分。结果:在ST段抬高组中,共检测出单支血管闭塞病变99例,占79.84%,两支或两支以上血管病变25例,占20.16%,其中侧支循环开放19例,开放率为15.32%。在ST段压低组中,共检测出单支血管非闭塞病变6例,占9.38%,两支或两支以上血管非闭塞病变56例,占87.50%,单支血管闭塞病变2例,占3.13%,其中侧支循环开放34例,开放率为53.13%。在ST段无偏移组中,单支血管闭塞病变15例,占75.00%,单支或多支血管非闭塞病变5例,占25.00%,其中侧支循环开放7例,开放率为35.00%。ST段抬高组、ST段无偏移组患者的冠脉狭窄程度以重度狭窄为主,ST段压低组患者的冠脉狭窄程度以中度狭窄为主,三组患者的轻度狭窄、中度狭窄、重度狭窄整体比较存在统计学差异(P0.05)。三组患者的疼痛评分、躯体受限评分、精神及活动评分整体比较具有统计学差异(P0.05),ST段压低组的上述评分均显著高于ST段抬高组和ST段无偏移组(P0.05)。结论:心电图ST段不同改变与急性心肌梗死患者冠脉造影病变密切相关,且ST段压低患者的预后通常较好。     

Localization of atherosclerotic lesions in the curving sites of human internal carotid arteries

We studied the distribution of the early atherosclerotic lesions in the curving sites of the human internal carotid arteries composed of the carotid siphon portion (part I) and carotid canal portion (part II). These early atherosclerotic lesions included a localized cloudy thickening with pallor, slight elevation, a non-fibrotic lesion and gray-white or yellowish-white, firm, elevated fibrous plaques. These lesions had the same pattern-distribution in each curving artery. Both were located in the distal regions from the middle of the inner curvature of parts I and II, where eddying fluid motions and directional change in the wall shear stress were considered to occur. In part I, there was a localized cloudy thickening in the younger subjects (average age: 22.8 years) rather than fibrous plaques (average age: 63.3 years). A positive correlation between the extent of the surface areas involved with fibrous plaques and the age of subjects was found in parts I and II. The extent of the surface areas involved with fibrous plaques was significantly greater in part I (26.9%) than in part II (7.85%). The radius of curvature was shorter in the former than in the latter. These results suggest that hemodynamic factors associated with flow in the curving sites of arteries may be important for the localization and progression of atherosclerotic lesions.     

Senile Cardiac Amyloidosis in The Dog

Thirty-two cases of senile cardiac amyloidosis from a routine necropsy material of 594 dogs were studied. The age of the affected dogs ranged from 10 to 16 years. Amyloid was observed in the intramural arteries and arterioles, predominantly in the ventricular myocardium. The vessels were often obturated with amyloid, and myocardial necroses and fibroses were common consequences of the vascular lesions. In three cases amyloid deposits were also observed in the main subepicardial coronary arteries. In contrast to man, only slight interstitial amyloid degeneration was found in four of the dogs observed. Amyloid in the mitral valves, tricuspid valves and aortic cusps was observed in six, two and three cases respectively. It was concluded that the distribution of senile cardiac amyloidosis in the heart of the dog differs considerably from that in man.     

Spontaneous Aortic Lesions in Fallow Deer (Dama Dama L)

In 19 out of 22 aortas from fallow deer, 15 months to 5½ years, aortic lesions were found. Three types of lesions were observed, fatty streaks were seen in 2, fibrous plaques in 15 and fibrous plaques with complicated lesions (calcification and acid mucopolysaccharides) in 2 of the aortas. Elastic tissue degeneration of the inner two thirds of the tunica media was frequently found in the aorta of the animals > 3½–5½ years of age. There was no statistical evidence for a correlation between age and frequency (P ~ 0.10) but a trend towards age dependence was seen. The percentage of involved surface was found to significantly increase (0.05 > P > 0.01) with age. Lesions were found to start in the abdominal aorta in young animals and to extend cranially to the thoracic aorta with age. The percentage of involved surface in different affected regions, comprising all age groups were, in the posterior abdominal portion, 10.5 %, in the anterior abdominal portion, 4.3 % and in the posterior thoracic portion, 1.04 %. The influence of hemodynamic flow upon the localization of the aortic lesions, the endothelial cell population density and the endothelial nuclear patterns were discussed.     

Disorders in the system of cyclic nucleotides in atherosclerosis: cyclic AMP and cyclic GMP content and activity of related enzymes in human aorta

Cyclic AMP and cyclic GMP content and activities of cyclic nucleotide metabolic enzymes were determined in intima and media of atherosclerotic and unaffected human aorta obtained shortly after death due to myocardial infarction. Cyclic AMP content in fatty streaks and atherosclerotic plaques was lower by three- and five-fold, respectively, as compared with uninvolved intima. Cyclic GMP level in atherosclerotic lesions was estimated to be three-fold higher than in grossly normal area. Basal activity of adenylate cyclase in fatty streaks and plaques was two- to six-fold lower than in unaffected intima. Besides, the ability of adenylate cyclase to be stimulated by the stable analogue of prostacyclin, carbacyclin, was suppressed in plaques. Guanylate cyclase activity in fatty streaks was 1.5- to three-fold higher than in normal tissue. The thiol-reducing agent, dithiothreitol, decreased the enzyme activity to normal level, suggesting the oxidative nature of guanylate cyclase activation in the lesion zone. There were no significant changes in cyclic AMP phosphodiestease activity in the regions of the atherosclerotic lesion. Cyclic GMP phosphodiesterase activity in atherosclerotic plaques was two-fold lower than in the intima of unaffected areas. We did not find differences in the content of cyclic nucleotides or related enzyme activities in the media of uninvolved areas of human aorta nor in the media underlying atherosclerotic lesions. Our findings suggest that development of human atherosclerotic lesions is accompanied by dramatic changes in the cyclic nucleotide metabolism featuring gradual hormonal receptor uncoupling from adenylate cyclase, activation of guanylate cyclase in fatty streaks and inhibition of cyclic GMP phosphodiesterase in plaques.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apoptotic macrophage-derived foam cells of human atheromas are rich in iron and ferritin, suggesting iron-catalysed reactions to be involved in apoptosis

We investigated the presence of low-molecular-weight iron and ferritin in human atheromas, and their possible relation to the apoptotic process. Arterial wall segments with fatty streaks were collected from coronary arteries and thoracic aortas of 12 clinical autopsy cases with general atherosclerosis. Normal appearing regions from the same cases together with normal coronary arteries from seven young forensic autopsy cases, without any sign of atherosclerosis, were used for comparison. Anti-CD68 (macrophage marker) and anti-ferritin antibodies were applied to serial sections of the arterial wall segments, fixed in formadehyde and embedded in paraffin wax, using an avidin-biotin complex (ABC) technique. Similarly, apoptotic cells were assayed by the TUNEL technique, while low-molecular-weight iron was cytochemically detected by autometallography. Cell counting and computerised image analysis were performed to compare the distribution of macrophages, ferritin- and iron-rich cells, and apoptotic cells in the intima, media, and adventitia of the arteries.

Pronounced ferritin accumulation, occurrence of lysosomal low-molecular-weight iron, and apoptosis mainly concerned CD68-positive cells (macrophages) in the atherosclerotic lesions. No ferritin- or CD68-positivity was found in normal coronary arteries from the young forensic-autopsy cases, while a moderate number of such cells were observed in the intima of normal looking vessel areas from the control cases. In the intima, cytosolic ferritin and low-molecular-weight iron with a lysosomal type distribution were found in many CD68-positive macrophages which frequently were surrounded by erythrocytes. A substantial number of apoptotic cells within the intima, media, and adventitia were registered in all atherosclerotic lesions examined, although mainly in the vulnerable macrophage-enriched areas of the atheroma shoulder.

We suggest that iron may occur within the cytosol, mainly bound in ferritin, but also in low-molecular weight, redox-active form within the acidic vacuolar apparatus of macrophages and macrophage-derived foam cells following erythrophagocytosis or phagocytosis of apoptotic cells. Low-molecular-weight iron within lysosomes, present due to degradation of iron-containing structures, such as ferritin, may partially become exocytosed and contribute to cell-mediated LDL-oxidation. Moreover, such lysosomal iron may also sensitise lysosomes to oxidative stress and induce apoptosis of macrophage/foam-cells that may result in instability and rupture of atherosclerotic plaques.     

Progression of coronary atherosclerosis relates to the onset of myocardial infarction in an animal model of spontaneous myocardial infarction (WHHLMI rabbits).

Recently, we developed myocardial infarction-prone WHHLMI rabbits from coronary atherosclerosis-prone WHHL rabbits (WHHLCA rabbits) by selective breeding. In this study, we examined the relation of atherosclerotic plaques to the onset of myocardial infarction. We examined myocardial lesions of 378 WHHL rabbits born between 1992 and 2000, and atherosclerosis lesions of 93 WHHLCA and 82 WHHLMI rabbits. The aortic lesions were evaluated as percent surface lesion area. The coronary lesions were evaluated as cross sectional narrowing using sections prepared at 500 or 1,000 microm intervals. Serum lipid levels were assayed with enzymatic methods. The cumulative incidence of fatal myocardial infarction between 11 and 35 months old was 90% in WHHLMI rabbits and 21% in WHHLCA rabbits, respectively. Selective breeding increased the serum cholesterol levels by about 200 mg/dl despite there being no changes in triglyceride levels. Aortic and coronary atherosclerosis progressed markedly in WHHLMI rabbits compared to WHHLCA rabbits. Especially, WHHLMI rabbits over 15 months old showed more than 90% cross sectional narrowing of the left circumflex arteries, main stem of the left coronary artery, and the origin portion of the right coronary artery. In addition, there were no gender differences in atherosclerotic lesions of both aortas and coronary arteries. In conclusion, the present study showed that marked progression of coronary atherosclerosis was probably associated with spontaneous development of myocardial infarction in WHHLMI rabbits.     

Natriuretic peptide system gene expression in human coronary arteries.

The natriuretic peptides (NPs) ANF, BNP, and CNP have potent anti-proliferative and anti-migratory effects on vascular smooth muscle cells (SMCs). These properties make NPs relevant to the study of human coronary atherosclerosis because vascular cell proliferation and migration are central to the pathophysiology of atherosclerosis. However, the existence and cytological distribution of NPs and their receptors in human coronary arteries remain undetermined. This has hampered the development of hypotheses regarding the possible role of NPs in human coronary disease. We determined the pattern of expression of NPs and their receptors (NPRs) in human coronary arteries with atherosclerotic lesions classified by standard histopathological criteria as fatty streak/early atherosclerotic lesions, intermediate plaques, or advanced lesions. The investigation was carried out using a combination of immunocytochemistry (ICC), in situ hybridization (ISH), and semi-quantitative polymerase chain reaction (PCR). Both by ICC and ISH, ANF was found in the intimal and medial layers of all lesions. BNP was highly expressed in advanced lesions where it was particularly evident by a strong ISH signal but weak ICC staining. CNP was demonstrable in all types of lesions, giving a strong signal by ISH and ICC. This peptide was particularly demonstrable in the endothelium, as well as in the SMCs of the intima, media, and vasa vasorum of the adventitia and in macrophages. By ISH, NPR-A was not detectable in any of the lesions but both NPR-B and NPR-C were found in the intimal and the inner medial layers. By RT-PCR, mRNA levels of all NPs tended to be increased in macroscopically diseased arteries, but only the values for BNP were significantly so. No significant changes in NPR mRNA levels were detected by PCR. In general, the signal intensity given by the NPs and their receptors by ICC or ISH appeared dependent on the type of lesion, being strongest in intermediate plaques and decreasing with increasing severity of the lesion. This study constitutes the first demonstration of NPs and NPR mRNAs in human coronary arteries and supports the existence of an autocrine/paracrine NP system that is actively modulated during the progression of atherosclerotic coronary disease. This suggests that the coronary NP system is involved in the pathobiology of intimal plaque formation in humans and may be involved in vascular remodeling.     

Endothelial calcium signaling in rabbit arteries and its local alterations in early-stage atherosclerosis

This study is to examine whether endothelial calcium signaling is different between atherosclerosis-prone thoracic aortas (TA) and atherosclerosis–resistant carotid arteries (CA) in normal rabbits and how it changes in early-stage atherosclerosis. Local endothelial calcium signaling was examined in arterial segments obtained from rabbits fed with normal or high-cholesterol diet for 1–4 weeks. Contrasting to normal CA, normal TA showed lower endothelial calcium signaling with more concentrated NF-κB in the endothelial nuclei. In the same hypercholesterolemic animal, fatty streak formation was much more prominent in TA than in CA. TA endothelial calcium signaling became augmented in the second week of hypercholesterolemia, being most pronounced in smooth regions adjacent to miniature fatty streaks. It was sporadically elevated even in regions away from any detectable TA fatty streak. When the entire TA was covered with fatty streaks in the fourth week of hypercholesteremia, endothelial calcium signaling returned to the original level. In comparison, CA endothelial calcium signaling was reduced around scattered fatty streaks. Reduced calcium signaling happened where CA fatty streaks were 150 μm long (covering 15–30 cells); and it extended to areas adjacent to larger fatty streaks. Moreover, NF-κB remained in the cytosol of endothelial cells covering CA fatty streaks. Our results indicate that inter-vascular differences in endothelial calcium signaling may provide partial explanation in their differential susceptibility in atherosclerosis.     

Shear strain in the adventitial layer of the arterial wall facilitates development of vulnerable plaques

Myocardial infarction and stroke are two of the leading causes of death and primarily triggered by destabilization of atherosclerotic plaques. Fatty streaks are known to develop at sites in the arterial wall where shear stress is low. These fatty streaks can develop into more advanced plaques that are prone to rupture. Rupture leads to thrombus formation, which may subsequently result in a myocardial infarction or stroke. The relation between shear stress on the inner (endothelial) layer of the arterial wall in relation to plaque development has been studied extensively. However, a causal relation between adventitial shear forces and atherosclerosis development has never been considered.Arterial stiffening increases with age and may facilitate an increase in shear strain in the adventitial layer, an axial shear between artery and surrounding tissue. In the adventitial layer, a large number of inflammatory cells and perivascular structures are present that are subjected to shear strain. Cyclic strain applied to endothelial cells stimulates neovascularisation via different pathways. The conduit arteries in the human body (e.g. coronary and carotid artery) have their own nutrition supply: the vasa vasorum, which is located in the adventitial layer and sprouts into the intimal layer when atherosclerotic plaque develops. Increased plaque neovascularisation makes the plaques more prone to rupture. Therefore we hypothesize that increased shear strain facilitates the development of vulnerable plaques by stimulation of atherosclerotic plaque neovascularisation that sprouts from the adventitial vasa vasorum. Validation of this hypothesis paves the road to the use of adventitial shear strain (measured using a noninvasive ultrasound technique) as risk assessment in plaque.     

Blood flow patterns in the proximal human coronary arteries: relationship to atherosclerotic plaque occurrence

Atherosclerotic plaques in human coronary arteries are focal manifestations of systemic disease, and biomechanical factors have been hypothesized to contribute to plaque genesis and localization. We developed a computational fluid dynamics (CFD) model of the ascending aorta and proximal sections of the right and left coronary arteries of a normal human subject using computed tomography (CT) and magnetic resonance imaging (MRI) and determined the pulsatile flow field. Results demonstrate that flow patterns in the ascending aorta contribute to a pro-atherosclerotic flow environment, specifically through localization of low and oscillatory wall shear stress in the neighborhood of coronary orifices. Furthermore, these patterns differ in their spatial distribution between right and left coronary arteries. Entrance effects of aortic flow diminish within two vessel diameters. We examined relationships between spatial distributions of wall shear stress and reports of plaque occurrence in the literature. Results indicate low wall shear stress is co-located with increased incidence of lesions, and higher wall shear stresses are associated with lesion-resistant areas. This investigation does not consider plaque progression or advanced lesions, inasmuch as the CFD model was developed from a normal individual and the clinical data used for comparisons were obtained from autopsy specimens of subjects who died from non-cardiovascular causes. The data reported are consistent with the hypothesis that low wall shear stress is associated with the localization of atherosclerotic lesions, and the results demonstrate the importance of aortic flow on flow patterns in the proximal segments of the coronary arteries.     

Estrogen replacement increases coronary artery distensibility in ovariectomized rats.

The effect of estrogen on the passive characteristics of arteries is not known. We hypothesized that estrogen would increase arterial distensibility as part of its protective effect on the vasculature. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. One group received a placebo (n = 6), while two other groups (n = 5 each) of rats received a 17beta-estradiol pellet (0.15 mg or 0.5 mg with 60-day release). After 4 weeks of estrogen replacement, coronary and mesenteric arteries (<200 microm diameter) were dissected and mounted on a dual-chamber arteriograph. Lumen diameter and wall thickness were measured in pressurized arteries. The relative changes in diameter (distensibility) as well as wall thickness per unit change in pressure were significantly increased (p < 0.05) in the coronary arteries of the 0.5 mg estradiol replaced rats compared with the ovariectomized control animals and the 0.15 mg estradiol replaced rats. Surprisingly, in the mesenteric arteries from the same animals, there was no difference in distensibility or pressure - wall thickness among the groups. This study provides experimental data of a novel hypothesis that estrogen may afford part of its protection through vascular remodeling of the coronary circulation.     

Duplex scanning of brachiocephalic arteries and multislice spiral computed tomography of coronary arteries in the comprehensive evaluation of the arteries in women with rheumatoid arthritis

Comprehensive examination was made in women (mean age 49.6 +/- 7.4 years) with rheumatoid arthritis diagnosed abnormalities of brachiocephalic and coronary arteries in 86% of cases. Duplex scanning of brachiocephalic arteries revealed changes in 82% of the women. 64-section spiral computed tomography established coronary artery abnormalities in 33% of cases. There were isolated changes in the brachiocephalic arteries in 50% of the patients, a concomitant lesion of the brachiocephalic and coronary arteries in 32%, and isolated changes in the coronary arteries in 4%. A direct correlation was found between the index of coronary artery calcification and the intima-media thickness of brachiocephalic arteries.     

Oxysterol profiles of normal human arteries, fatty streaks and advanced lesions.

OBJECTIVE: Human atherosclerotic lesions of different stages have quantitative differences in cholesterol and oxysterol content, but information on the oxysterol profile in fatty streaks is limited. This study aims to provide more detailed oxysterol quantification in human fatty streaks, as well as normal aorta and advanced lesions. METHODS: A newly adapted method was used, including oxysterol purification by means of a silica cartridge; and it was ensured that artifactual oxysterol formation was kept to a minimum. Cholesterol and oxysterols were estimated by GC and identification confirmed by GC-MS in samples of normal human arterial intima, intima with near-confluent fatty streaks and advanced lesions, in necropsy samples. RESULTS: The oxysterols 7 alpha-hydroxycholesterol, cholesterol-5 beta, 6 beta-epoxide, cholesterol-5 alpha, 6 alpha-epoxide, 7 beta-hydroxycholesterol, 7-ketocholesterol and 27-hydroxycholesterol (formerly known as 26-hydroxycholesterol) were found in all the lesions, but were at most very low in the normal aorta, both when related to wet weight and when related to cholesterol. Most components of the normal artery showed some cross-correlation on linear regression analysis, but cross-correlations were weaker in the fatty streaks and advanced lesions. However, in fatty streak there was a marked positive correlation between 27-hydroxycholesterol and cholesterol. CONCLUSION: The findings confirm that oxysterols are present in fatty streaks and advanced lesions and may arise from different cholesterol oxidation mechanisms, including free radical-mediated oxidation and enzymatic oxidation.     

Immunoscintigraphy for detecting acute myocardial infarction without electrocardiographic changes.

OBJECTIVE--To establish whether immunoscintigraphy with antibody to myosin may detect acute myocardial infarction without electrocardiographic changes. DESIGN--Prospective study of patients with suspected acute myocardial infarction or unstable angina with cardiac imaging with 111indium myosin antibody, estimation of cardiac enzyme concentrations, electrocardiography, 201thallium imaging, and radionuclide ventriculography. SETTING--Coronary care unit in a district general hospital. PATIENTS--119 Consecutive patients with suspected acute myocardial infarction or unstable angina. Patients with cardiomyopathy, myocarditis, valvular heart disease, myocardial infarction or cardiac surgery in the previous two weeks or with left bundle branch block and women of childbearing age were excluded. RESULTS--Of 75 patients with suspected acute myocardial infarction, seven had no diagnostic electrocardiographic changes despite normal conduction patterns. Immunoscintigraphy with myosin antibody disclosed necrosis in all seven patients, which was localised in regions supplied by diseased coronary arteries in all but one. Six patients had abnormal images on 201thallium imaging, and all seven had abnormal wall motion at the site of antibody uptake. One patient with minimal left main stem and right coronary artery atheroma had uptake of antibody at two discrete sites. CONCLUSIONS--Immunoscintigraphy with antibody to myosin confirms myocardial infarction in the absence of electrocardiographic changes and discloses the site of infarction.