Extent Of Atherosclerotic Lesions Research Articles

Increased carotid intima media thickness and cardiac biomarkers in HIV infected children

To assess carotid intima media thickness (IMT) and cardiac biomarkers in HIV infected children on antiretroviral therapy (ART). This was a single site, cross sectional, controlled observational study. We assessed carotid IMT, homocysteine, high-sensitivity C-reactive protein and myeloperoxidase levels in HIV infected children on stable ART for >or= 6 months. Carotid IMT was reported as internal carotid artery (ICA) and common carotid artery (CCA) thickness; left and right sides were measured separately. Groups were compared using appropriate two-sample tests. Of the 62 subjects enrolled, 31 were HIV positive (50%), 66% were female, and 69% were African-American. Median CD4% was 32% and 26 patients (84%) had HIV-1 RNA< 400 copies/ml. Sixteen patients had been taking protease inhibitors for a median duration of 27 months. None had hypertension or smoked. HIV infected children had higher HOMA-IR, waist-to-hip ratio, cholesterol, triglycerides, myeloperoxidase and lower homocysteine levels. Left and right CCA IMT, and left and right ICA IMT were significantly higher in the HIV infected group. Significant predictors of carotid IMT measurements in uninfected controls were body mass index and homocysteine, but only the duration of ARV therapy was predictive of IMT in the HIV infected group. Higher levels of carotid IMT and some cardiac markers were found in ART treated HIV infected children when compared to matched uninfected controls. These results suggest that HIV infected children receiving ART may be at increased risk of cardiovascular disease.

Granulocyte Colony-Stimulating Factor and Granulocyte Macrophage Colony-Stimulating Factor Exacerbate Atherosclerosis in Apolipoprotein E–Deficient Mice

Recent studies have suggested a potential contribution of bone marrow-derived progenitor cells to vascular repair. Preliminary clinical studies have explored the possibility that mobilization of progenitor cells with granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can affect vascular repair. However, it is not known whether the short-term administration of G-CSF or GM-CSF exerts beneficial effects on atherosclerosis. Apolipoprotein E-deficient mice were treated with either GM-CSF or G-CSF at a dose of 10 microg x kg(-1) x d(-1) s.c. administered daily for 5 days per week on alternating weeks for a total of 20 doses over an 8-week treatment period. We found that in animals maintained on a high-fat diet, both G-CSF and GM-CSF actually demonstrated an increase in atherosclerotic lesion extent. The increase in atherosclerotic extent was not associated with an increase in either inflammatory cells or expression of proinflammatory genes. Interestingly, adventitial vascularity significantly increased, suggesting a mechanistic role for vasa vasorum neovascularization. These findings demonstrate that in this animal model of atherosclerosis, not only did administration of G-CSF or GM-CSF fail to demonstrate any beneficial therapeutic effect, but both resulted in a worsening of atherosclerosis.

Vascular cell adhesion molecule-1: a viable therapeutic target for atherosclerosis?

Atherosclerosis is now well recognised as a chronic inflammatory process which may ultimately lead to myocardial infarction, stroke and peripheral vascular disease. The role of inflammation in the pathogenesis of atherosclerosis has lead to interest in developing therapies that target vascular inflammation. Leucocytes play a key role during atherosclerotic plaque development. Activated vascular endothelium expresses vascular cell adhesion cell molecule-1 (VCAM-1), a member of the adhesion molecule superfamily, to which monocytes and lymphocytes can bind. These inflammatory cells can then move through the endothelium by diapedesis and release cytokines and enzymes, important components in the progression of the lesion. Researchers have demonstrated that the extent of atherosclerotic lesions is significantly reduced in animal models with decreased VCAM-1 expression. VCAM-1 has therefore been identified as a potential anti-inflammatory therapeutic target, the hypothesis being that reduced expression of VCAM-1 will slow the development of atherosclerosis. Succinobucol (AGI-1067), an anti-oxidant compound also capable of inhibiting VCAM-1 gene expression, is an example of such an agent and is currently being investigated in a phase III cardiovascular end-point trial due to report in 2007. If the results are positive, further investigations should derive to what extent blockade of VCAM-1 by succinobucol, rather than its other effects, accounts for the reduction in vascular events.

Cyclooxygenase-1 Deficiency in Bone Marrow Cells Increases Early Atherosclerosis in Apolipoprotein E– and Low-Density Lipoprotein Receptor–Null Mice

Cyclooxygenase-1 (COX-1) has been implicated in the pathogenesis of atherothrombosis and is expressed by the major cell types of atherosclerotic lesions. COX-1-mediated platelet thromboxane (TX) production has been proposed to promote both early atherosclerosis and thrombosis. Here, we examined the impact of COX-1 deficiency in bone marrow-derived cells on early atherogenesis in the mouse. LDL receptor (LDLR)(-/-) and apolipoprotein E (apoE)(-/-) recipient mice were lethally irradiated and transplanted with COX-1(-/-) bone marrow. Mice reconstituted with COX-1(-/-) marrow had nearly complete (99.7%) loss of platelet TXA2 and significantly suppressed levels of macrophage and urinary TXA2 metabolites. Serum lipid levels and lipoprotein distributions did not differ between recipients reconstituted with COX-1(+/+) and COX-1(-/-) marrow. Surprisingly, the extent of atherosclerotic lesions in both LDLR(-/-) and apoE(-/-) mice reconstituted with COX-1(-/-) marrow was increased significantly compared with control mice transplanted with COX-1(+/+) marrow. Peritoneal macrophages isolated from LDLR(-/-) mice reconstituted with COX-1(-/-) marrow had increased lipopolysaccharide-induced levels of COX-2 mRNA and protein expression. Fetal liver cell transplantation studies revealed a 30% increase in atherosclerosis in COX-1(-/-)-->LDLR(-/-)mice compared with COX-1(+/+)-->LDLR(-/-)mice, whereas the extent of atherosclerosis was unchanged in COX-1(-/-)/COX-2(-/-)-->LDLR(-/-)mice. COX-1 deficiency in bone marrow-derived cells worsens early atherosclerosis in apoE(-/-) and LDLR(-/-) mice despite virtual elimination of platelet TX production. These data demonstrate that platelet TX production does not aggravate early atherosclerotic lesion formation and that upregulation of COX-2 expression in COX-1(-/-) macrophages is proatherogenic.

Dietary phytosterols reduce probucol-induced atherogenesis in apo E-KO mice

We have previously shown strong pro-atherogenic effects of probucol in apolipoprotein E-knockout (apo E-KO) mice. The aims of the present study were to investigate whether (a) dietary phytosterols reduce probucol-induced atherogenesis and (b) beneficial interactions exist between these agents. Male apo E-KO mice fed with an atherogenic diet supplemented with phytosterols or probucol or their combination for 14 weeks. Single therapy with either phytosterols or probucol resulted in a 25% reduction in plasma total cholesterol (TC) concentrations as compared to the control group. The effects of the combination therapy were more profound (60% reduction). While phytosterols reduced atherogenesis by 60%, probucol caused an increase of 150% in atherogenesis. Addition of phytosterols to probucol substantially reduced pro-atherogenic effects of probucol. This was associated with improved high density lipoprotein (HDL) concentrations. The ratio of TC to HDL cholesterol was markedly reduced in the combination therapy group as compared to the probucol-treated group. A strong positive association between the ratio of TC to HDL cholesterol and the extent of atherosclerotic lesions was observed. The coronary arteries of the probucol-treated group showed various stages of atherogenesis from infiltration of monocytes into intima to complete occlusion of the vessel by atheromatous lesions. Such pathological findings were not observed in the combination therapy group. Approximately 40% of the mice in the probucol-treated group and 10% of the animals in the combination therapy group developed skin lesions. Further studies warrant the investigation of the underlying mechanisms of the observed beneficial interactions between dietary phytosterols and probucol.

High sodium intake increases vascular superoxide formation and promotes atherosclerosis in apolipoprotein E‐deficient mice

Hypertension is a major risk factor for atherosclerosis. We tested the hypothesis whether high salt intake aggravates endothelial dysfunction and promotes atherosclerosis in apolipoprotein E‐deficient mice (ApoE−/− mice) and their littermate controls (C57Bl/6 mice). The role of increased oxidative stress was also examined. A high‐salt diet (NaCl 7%) for 12 weeks increased blood pressure and induced cardiac hypertrophy and albuminuria more pronouncedly in ApoE−/− mice compared with C57Bl/6. Endothelium‐dependent vascular relaxation in response to acetylcholine was almost maximally impaired in ApoE−/− mice during a normal sodium diet. A high‐salt diet did not further impair NO‐mediated vascular relaxation. A high‐salt diet also markedly attenuated endothelium‐dependent relaxation in C57Bl/6 mice. Preincubation with the superoxide scavenger Tiron normalized endothelial function almost completely in both mice strains indicating the central role of increased oxidative stress in the pathogenesis. Aortic superoxide production and the extent of atherosclerotic lesions were greater in ApoE−/− mice on a normal‐salt diet compared with C57Bl/6. The high‐salt diet increased vascular superoxide formation and promoted atherosclerosis in ApoE−/− mice. Changes in dietary salt intake did not influence serum lipids in either mouse strains. Our findings suggest a detrimental role for high salt intake in the development of atherosclerosis and underscore the importance of increased oxidative stress in the pathogenesis salt‐induced vascular damage.

Interrelation between the extent of atherosclerosis in the thoracic aorta, carotid intima-media thickness and the extent of coronary artery disease

Intima-media thickness (IMT) of the common carotid artery and atherosclerosis of the thoracic aorta have been shown to correlate with coronary artery disease (CAD). This study compares the relation between wall changes in the thoracic aorta and the carotid arteries and the angiographic severity and extent of atherosclerotic lesions in the coronary arteries in patients with verified CAD. Atherosclerotic wall changes in the carotid arteries and the thoracic aorta were measured by B-mode ultrasonography and transesophageal echocardiography (TEE), respectively, in 37 subjects aged 65 ± 10 years with angiographically verified CAD. The mean value of the common carotid IMT of the right and left sides was 0.87 ± 0.21 mm. All subjects had carotid plaques. TEE detected grades II–IV atherosclerotic plaques in the thoracic aorta in 32 of the 37 (86%) patients. A significant correlation was seen between the extent of coronary artery stenosis and aortic plaques score ( r = 0.46, p = 0.008). Mean carotid IMT was also significantly correlated with coronary artery stenosis extent score ( r = 0.44, p = 0.007). Moreover, a significant correlation was seen between the aortic plaque score and the mean carotid IMT ( r = 0.39, p = 0.02). In conclusion, we found a clear and significant relationship between wall changes in the thoracic aorta, common carotid IMT and the angiographic extent of coronary artery stenosis in patients with severe CAD. These findings indicate a potential of B-mode ultrasonography of the carotid arteries and transesophageal echocardiographic aortic examination in the diagnostic and prognostic evaluation of patients with suspected CAD.

Cardiovascular Health Promotion in the Schools

Cardiovascular disease (CVD) is a major cause of morbidity and premature mortality in men and women in the United States, most of the industrialized world, and many developing countries.1 Primary prevention of CVD beginning in early childhood is supported by extensive evidence culled from epidemiological, clinical, and laboratory studies.2–16 Taken together, these data provided the impetus for the American Heart Association (AHA) Guidelines for Primary Prevention of Atherosclerotic Cardiovascular Disease Beginning in Childhood17 and support the need for population-based approaches to cardiovascular health promotion and risk reduction. Specifically, the population-based approach, which is aimed at modifying the food and physical activity environments of children, is an important concomitant to the high-risk approach because without the proper environment, the high-risk strategy cannot be optimally implemented. School health programs initiated in preschool and extending through high school have the potential to influence the cardiovascular health of the majority of US children and youth. Toward this goal, this statement is intended for health and education professionals, child health advocates, policymakers, and community leaders who are interested in optimizing the school environment as an integral part of population-based strategies designed to promote cardiovascular health for all US children and youth and reduce the risk and public health burden of CVD. Several lines of evidence underscore the importance of primary prevention of CVD beginning in childhood and the need for population-based approaches to cardiovascular health promotion and risk reduction. Autopsy studies (after the unexpected deaths of children and youth)2–5 document significant positive associations between established risk factors and the presence and extent of atherosclerotic lesions in the aorta and coronary arteries of children and youth. Specifically, data from the Bogalusa Heart Study3,4 and the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)2,5 study link potentially modifiable risk factors, including atherogenic …

Effect of a taurine treatment on the regression of existing atherosclerotic lesions in rabbits fed on a high-cholesterol diet.

We studied whether taurine has any regressive effect on existing atherosclerotic lesions and lipid peroxidation in rabbits fed on a high-cholesterol (HC) diet. The cholesterol, triglyceride, malondialdehyde (MDA) and diene conjugate (DC) levels, as well as the aortic histopathological findings were examined in rabbits that had been fed on a cholesterol-containing diet for 8 months [0.5% cholesterol (w/w) for 3 months and subsequently 0.25% cholesterol (w/w) for 5 months], and then for a further 4 months on a normal diet with or without taurine treatment [1% (w/v) in the drinking water]. High levels of lipid and lipid peroxide induced by the HC diet were observed to decline in the plasma, liver and aorta of atherosclerotic rabbits, as well as a slight retardation in aortic atherosclerotic lesions during the regression period. Although no significant differences in the lipid and lipid peroxide levels in the plasma and aorta were found between the regressed groups with or without the taurine treatment, the extent of atherosclerotic lesions in the aorta was less in the taurine-treated regressed group than in the non-treated regressed group. However, the liver MDA and DC levels were lower in the regressed rabbits with the taurine treatment in the non-treated group. These results indicate that the taurine treatment may accelerate the regression of cholesterol-induced atherosclerotic lesions in rabbits without having any effect on the plasma and aorta lipid and lipid peroxide levels.

Serum chitotriosidase activity is increased in subjects with atherosclerosis disease.

This study was undertaken to analyze the relation between serum activity of chitotriosidase enzyme, a protein synthesized exclusively by activated macrophages, and atherosclerotic lesion extent in subjects with atherothrombotic stroke (ATS) and in subjects with ischemic heart disease (IHD). We assayed the serum chitotriosidase activity and a common chitotriosidase gene polymorphism that causes deficiency in chitotriosidase activity in 3 Spanish populations, ATS (n=153), IHD (n=124), and control (n=148) subjects. Statistical differences were found in serum chitotriosidase activity between ATS (88.1+/-4.6 nmol/mL. h, P<0.0001) and IHD subjects (79.0+/-6.3, P=0.002) versus control group (70.9+/-5.2). These observed differences were not attributable to a distinct allelic or genotype distribution. The extension of the atherosclerotic lesion in carotids of ATS subjects was measured by duplex sonography. Chitotriosidase activities were 66.9+/-9.6, 88.7+/-8.3, and 107.7+/-11.8 for subjects with carotid stenosis <or=30%, 31% to 60%, and >60%, respectively. Statistical differences were observed between subjects with major and intermediate stenosis grade compared with subjects with minor stenosis, P=0.005 and P=0.016, respectively. Serum chitotriosidase activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker.

American heart association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood

Atherosclerotic cardiovascular disease remains the leading cause of both death and disability in North America. Evidence that most cardiovascular disease is preventable led to development of the American Heart Association’s initial “Guide to the Primary Prevention of Cardiovascular Disease” in 1996 and the updated version in 2002. Those guidelines do not address prevention in children, a group for whom primary prevention should hold the most promise. Emergence of multiple lines of evidence with regard to the importance of known risk factors for atherosclerotic disease in children and young adults has provided the impetus to develop guidelines for primary prevention in this young population. Pathological studies have shown that both the presence and extent of atherosclerotic lesions at autopsy after unexpected death of children and young adults correlate positively and significantly with established risk factors, namely low-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, body mass index, and presence of cigarette smoking. Findings from the Bogalusa study indicate that as the number of cardiovascular risk factors increases, so does the pathological evidence for atherosclerosis in the aorta and coronary arteries beginning in early childhood. Electron beam computed tomography of coronary artery calcium and increased carotid artery intima-media thickness, an ultrasound measure of carotid artery atherosclerosis, have been evaluated in 29- to 39-year-olds monitored from 4 years of age. Significant risk predictors for coronary artery calcium were obesity and elevated blood pressure in childhood and increased body mass index and dyslipidemia as young adults. Multiple epidemiological studies have demonstrated a disturbing increase in the prevalence of obesity beginning in childhood, with at least 22% of 6- to 17-year-olds diagnosed as overweight. This is a cause for particular concern because of the strong association between obesity and hypertension, dyslipidemia, and type II diabetes mellitus beginning in childhood. Long-term follow-up studies have demonstrated …

Atherogenesis inhibition induced by magnesium-chloride fortification of drinking water.

Magnesium (Mg) modulates blood lipid levels, atherogenesis, and atherosclerosis in rabbits, when supplemented to diet. We have recently reported that a high concentration (50 g/L) of Mg sulfate fortification of drinking water attenuates atherogenesis in male and female LDL-receptor-deficient mice fed a high-cholesterol diet. The aims of the current study were to examine whether lower concentrations and another Mg salt could also have such an antiatherogenic effect. Thirty male LDL-receptor-deficient mice were divided into three groups (n=10 in each group). The mice received either distilled water or water fortified with 0.83 g or with 8.3 g Mg-chloride per liter. In the first (27 wk) and second (5 wk) stages of the experiment, the mice received normal chow and Western-type diet, respectively. Blood was drawn for determination of plasma Mg, calcium, and lipid levels. The extent of atherosclerotic lesions was determined at the aortic sinus. Magnesium-chloride fortification of drinking water did not result in higher plasma Mg concentrations, whereas a trend toward lower plasma calcium concentrations did not reach statistical significance. Even though plasma lipid levels were similar at the beginning and the end of the study, there were decreased plasma cholesterol and triglyceride levels in the Mg groups after stage I. The atherosclerosis extent at the aortic sinus was significantly decreased in the 8.3-g Mg-chloride/L group (23,437 +/- 10,083 micron2) compared with the control group (65,937 +/- 31,761 microm2). There was also a trend toward lower atherosclerosis extent at the aortic sinus in the 0.83-g Mg-chloride/L group. An additional Mg salt (Mg-chloride) fortification of drinking water is capable of inhibiting atherogenesis in male LDL-receptor-deficient mice. That is done in a lower concentration of Mg than previously reported.

Beta2-glycoprotein I and atherosclerosis.

Appreciation of the multifactorial nature of atherosclerosis requires a broad understanding of the mechanisms that underlie its pathogenesis. Autoimmune factors have recently been shown to be associated with the initiation and progression of atherosclerosis. In this context, modified lipoproteins were explored because of their de-novo occurrence within the vessel wall, and heat shock proteins are also being reported by several authors as triggers of autoimmune-like reactions that associate with atherosclerosis. Antiphospholipid antibodies in general and anti-beta2-glycoprotein I (beta2GPI) antibodies in particular have been shown to confer a procoagulant tendency in humans, either in the presence or the absence of the antiphospholipid syndrome. These findings and the ability of antibodies to beta2GPI to activate monocytes and endothelial cells led us to consider whether they are proatherogenic. In a series of studies it was shown that inducing an immune response to beta2GPI in atherosclerosis-prone mice accelerated atherosclerosis. We also demonstrated the abundance of beta2GPI in the atheroma, in conjunction with immunopotent cells. Moreover, when beta2GPI-reactive lymph node and spleen cells were transferred to LDL-receptor-deficient mice they promoted fatty streak formation, proving a direct proatherogenic role for beta2GPI-specific lymphocytes. Perhaps the most important implications of the existence of antigen-specific immune reactions within the atheroma is the ability to exploit them for the purpose of selective immunomodulation. Indeed, we have found that inducing immunological tolerance to beta2GPI by prior oral feeding with the antigen resulted in a significant reduction in the extent of atherosclerotic lesions. Thus, beta2GPI is a candidate player in the atherosclerotic plaque, and can possibly be employed as an immunomodulator of plaque progression.

The combined effect of inhibiting both ACAT and HMG-CoA reductase may directly induce atherosclerotic lesion regression

We hypothesized that coadministration of avasimibe and simvastatin would limit size, composition and extent of atherosclerotic lesions and potentially promote lesion regression, since bioavailable ACAT inhibitors decrease monocyte-macrophage enrichment and HMG-CoA reductase inhibitors limit smooth muscle cell migration and proliferation. Male New Zealand white rabbits were sequentially fed a 0.5% cholesterol, 3% peanut oil, 3% coconut oil diet for 9 weeks and a chow-fat diet for 6 weeks prior to drug administration. A time zero control group was necropsied prior to drug administration and the progression control was fed various diets but untreated. Avasimibe (10 mg/kg), simvastatin (2.5 mg/kg) or combination of avasimibe (10 mg/kg) with simvastatin (2.5 mg/kg) were administered in the chow-fat diet for 8 weeks. Plasma total cholesterol exposure was unchanged by avasimibe but was reduced 21% by both simvastatin alone and in combination with avasimibe. Combination of avasimibe and simvastatin decreased VLDL-cholesterol exposure by 56%. VLDL+IDL lipid composition was similar in the progression control and simvastatin-treated animals. Administration of avasimibe alone or in combination with simvastatin reduced the cholesteryl ester fraction and increased the triglyceride fraction to comparable extents. Relative to the progression control, avasimibe plus simvastatin markedly decreased thoracic aortic cholesteryl ester content and lesion coverage by 50% and aortic arch lesion size and macrophage area by 75 and 73%, respectively. With respect to lesion regression, avasimibe+simvastatin decreased aortic arch lesion size by 64% and monocyte-macrophage area by 73% when compared to time zero. Based on these data, we conclude that despite changes in plasma total and lipoprotein cholesterol exposure and lipoprotein composition comparable to monotherapy, inhibition of both ACAT and HMG-CoA reductase may not only directly blunt lesion progression but also promote regression of pre-established atherosclerotic lesions.

Coronary risk factors in Turkish schoolchildren: randomized cross-sectional study.

There is a strong association between the extent of atherosclerotic lesions in aorta and coronary arteries and antemortem risk factors in children and young adults. Cardiovascular diseases are the most common cause of death in adults in Turkey. However, the data about the extent of coronary risk factors in Turkish children is very limited. The aim of this cross-sectional study was to investigate the prevalence of coronary risk factors in Turkish schoolchildren living in Eskişehir, Turkey. A randomly selected population of 4026 schoolchildren, aged between 7 and 18 years, residing in urban and rural parts of Eskişehir were evaluated for coronary risk factors, using previously predicted risk threshold values. Hypertension was found in 4.8% of the girls and 3.8% of the boys, 14.9% of the girls and 10.8% of the boys had abnormal lipid values, 18.2% of the girls and 26.4% of the boys had elevated total body fat percentages, 20.7% of the girls and 14.5% of the boys had physical inactivity and 3.8% of the girls and 11.4% of the boys were regular smokers. Urban children had higher rates of hypercholesterolemia; however, rural children had higher rates of physical inactivity. When the modifiable risk factors were considered, excluding family history, 47.7% of the children had at least one risk factor and 11.7% of them exhibited two or more risk factors. Turkish schoolchildren living in Eskişehir had considerably high levels of coronary risk factors. The interventional measures established in childhood, during which the lifestyle and habits responsible for coronary heart diseases are acquired, will be very effective for preventing and modifying the risk factors predisposing children to coronary heart disease.

Modulation of the regression of atherosclerosis in the hamster by dietary lipids: comparison of coconut oil and olive oil.

The Golden Syrian hamster (Mesocricetus auratus) has been shown to be a useful model of both human lipoprotein metabolism and the development of atherosclerosis. We report the effects of dietary lipids on the progression and regression of atherosclerosis in this model. In the first study, hamsters fed on coconut oil (150 g/kg diet) and cholesterol (30 g/kg diet) developed lipid-rich lesions in the ascending aorta (0.28 (SD 0.14) mm2) and aortic arch (0.01 (SD 0.01) mm2) after 4 weeks that continued to progress over the next 8 weeks (0.75 (SD 0.41) mm2 and 0.12 (SD 0.11) mm2 for the ascending aorta and aortic arch respectively). Removal of cholesterol from the diet halted this progression. Furthermore, in animals fed on olive oil in the absence of added cholesterol, plasma LDL-cholesterol concentrations were lower (P < 0.05) and the extent of atherosclerotic lesions was reduced (P < 0.001 for both regions of the aorta) compared with animals fed on coconut oil (with no added cholesterol). In a second study, animals were fed on the atherogenic diet for 10 weeks, transferred to diets containing either coconut oil (150 g/kg diet) or olive oil (150 g/kg diet) without added cholesterol and monitored for up to 16 weeks. In the ascending aorta, lesion size doubled in animals fed on coconut oil but stabilized in those fed on olive oil. In the aortic arch, lesion size decreased linearly (P < 0.05, P < 0.001 for coconut oil and olive oil respectively) with the greatest reduction being seen in the olive-oil-fed animals (P < 0.05). Again, progression and regression of atherosclerosis appeared to reflect the relative concentrations of LDL-cholesterol and HDL-cholesterol in the plasma. We conclude that the male Golden Syrian hamster represents a useful model of dietary induced regression as well as progression of atherosclerosis.

Apolipoprotein E and atherosclerosis in Greenland Inuit

Arterial, liver, and serum specimens were collected from Greenland Inuit at autopsy and apolipoprotein E genotyping was done on 42 females (mean age=61.3 years) and 56 males (mean age=56.8 years). Estimates of the allele frequencies of the apo E, derived from the observed frequencies of the six common apolipoprotein E genotypes, are E2: 0.015±0.009; E3: 0.776±0.030; and E4: 0.209±0.029. No significant difference was found between these frequencies and those previously reported for Greenland Inuit, Canadian Inuit, or Alaska natives; however, differences were observed in comparison with frequencies reported for Japan, Norway, Sweden, USA-Blacks and USA-Whites. Anthropometric data (body mass index, panniculus adiposus thickness), blood analyte levels (total serum cholesterol, HDL-cholesterol, LDL+VLDL-cholesterol, and glycohemoglobin), and prevalence and extent of atherosclerotic lesions in the aorta and coronary arteries were analyzed for any associations with apolipoprotein E genotype. The occurrence of apolipoprotein E2 alleles are very rare and the E4 alleles are slightly more frequent in the Greenland Inuit population as compared to other populations. No significant association between apolipoprotein E genotypes and the extent of atherosclerotic lesions in the aorta and coronary arteries were found, and there does not appear to be any strong evidence for an association of either serum lipids, glycohemoglobin levels, or adiposity measurements to apolipoprotein E genotype in Greenland Inuit.

Estrogen-mediated increases in LDL cholesterol and foam cell-containing lesions in human ApoB100xCETP transgenic mice.

The murine double transgenic mouse expressing both human apoB100 and cholesteryl ester transfer protein (CETP), has been used as a model to understand the effects mediated by various therapeutic modalities on serum lipoproteins and on atherosclerotic lesion progression. In the present study the effects of estrogen therapy on serum lipoproteins were investigated after mice were placed on an atherosclerotic diet. The daily oral administration of 20 or 100 microg/kg of 17 alpha-ethinyl estradiol resulted in a significant, dose-dependent increase in LDL cholesterol over a 20-week regimen. These differences were apparent by 6 weeks and further increases were observed through the 20-week period. Although CETP did result in a reduction in total HDL, estrogen did not have any impact on the amount of CETP activity associated with the HDL particles. The significant increase in LDL cholesterol was associated with increases in the amount of apoB100 and B48 and apoE-containing particles. Hepatic apoB message levels, however, were not different between the experimental groups. Although the extent of atherosclerotic lesions was modest, <0.5% of the aortic surface area in the vehicle group, the high-dose estrogen group, showed an increase in lesion area consistent with the elevation in LDL cholesterol. These lesions, primarily restricted to the aortic root and aortic semilunar valves, were more intensely stained with Oil Red O in the high-dose estrogen group when compared with the vehicle controls.

Regional characteristics of the harmonic components of the pressure pulse wave in the atherosclerotic aorta of the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit

Abstract We investigated the relationship between the severity and extent of atherosclerotic lesion and harmonic components of the pressure pulse waves at different aortic regions in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit aged 10∼12 months. Frequency spectra of the pressure pulse waves recorded at nine positions from the ascending aorta to the left iliac artery were obtained for the first (Hc1) to fifteenth (Hc15) harmonic components with fast Fourier transformation. The amplitudes of Hc1, Hc2 and Hc3 progressively increased with distance along the aorta from the heart as observed in the normal rabbit, whereas the amplitudes of Hc4 to Hc6 were very slightly increased towards the peripheral aortic position. At any given aortic position, Hc1 and Hc2 showed higher amplitude in the KHC rabbit than in the normal rabbit except at the aortic region between the ascending aorta and the proximal thoracic aorta, in which sclerotic lesion was more severe and extensive than in any other aortic regions. These results suggest that the increased amplitude of the pressure pulse wave `peaking', apparent in the peripheral aortic region of the KHC rabbit, was mainly caused by the increase in the amplitudes of Hc1 and Hc2 of the pulse wave, and that the decrease in the amplitudes of Hc2 and Hc3 in the aortic arch was related to the severity and extent of atherosclerotic lesion.

Multiplane transoesophageal echocardiographic detection of thoracic aortic plaque is a marker for coronary artery disease in women

Objective: This study was conducted to examine if the multiplane transoesophageal echocardiographic detection of atherosclerotic plaque in the thoracic aorta could predict the absence or the presence and the severity of significant coronary artery disease in women. Its association with coronary disease is attractive and may have great influence on foregoing routine preoperative cardiac catheterization in patients with valvular heart disease but no data are available in women. Methods: Clinical and angiographic features and transoesophageal echocardiographic findings were prospectively analysed in 111 women. Results: In 24 women with significant coronary disease, 20 had thoracic aortic plaque on transoesophageal echocardiographic studies. In contrast, aortic plaque existed in only 12 of the remaining 87 women with normal or mildly abnormal coronary arteries. Therefore, the presence of aortic plaque had a sensitivity of 83%, a specificity of 86%, a positive and negative predictive values of 62% and 95%, respectively for the detection of significant coronary disease. There was a significant relation between the severity and the extent of atherosclerotic lesions and the angiographic coronary score ( P<0.0001). Multivariate logistic regression analysis revealed that aortic plaque was the most significant independent marker of coronary disease (odds ratio=27.9; 95% confidence interval=5.5–131.6; P<0.0001). Conclusions: This prospective study indicates that multiplane transoesophageal echocardiographic examination of thoracic atherosclerotic plaque is a marker for coronary disease in women and especially a powerful predictor of absence of significant coronary artery disease. Transoesophageal echocardiographic aortic examination might be used with risk factors and angina symptoms to discuss the need for preoperative coronary angiography in women with valvular heart disease.