Atherosclerotic Plaques In Rabbits Research Articles

Oral rapamycin attenuates inflammation and enhances stability of atherosclerotic plaques in rabbits independent of serum lipid levels

Atherosclerotic plaque rupture and thrombosis are the main cause of acute coronary syndrome. The study was aimed to test the hypothesis that oral administration of rapamycin may attenuate inflammation, inhibit progression and enhance stability of atherosclerotic plaques. Thirty New Zealand rabbits were subjected to balloon-induced endothelial injury of the abdominal aorta and were fed a diet of 1% cholesterol for 20 weeks. From week 9 to week 20, the animals were treated with oral rapamycin (0.5 mg x kg(-1) x day(-1); group A), oral simvastatin (5 mg x kg(-1) x day(-1); group B) and no drugs (group C). At the end of week 20, all rabbits were challenged with injection of Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathological, immunohistochemical and gene expression studies were performed. Rapamycin significantly increased the thickness of the fibrous caps and decreased plaque vulnerability index in group A rabbits. Serum lipid levels were higher whereas plaque burden was lower in group A than in group B (P < 0.05). The incidence of plaque rupture in group A (0%) and group B (0%) was significantly lower than that in group C (56.0%, P < 0.05). Oral administration of rapamycin effectively attenuated inflammation, inhibited progression and enhanced stability of atherosclerotic plaques in rabbits, without altering serum lipid levels. Our findings suggest a novel approach to the treatment of atherosclerosis.

Multimodality Cardiovascular Molecular Imaging, Part I

In Part I of this consensus article, the imaging methodology, evolving imaging technology, and development of novel targeted molecular probes relevant to the developing field of cardiovascular molecular imaging were reviewed. Novel reporter gene and reporter probe imaging approaches for tracking of cardiac transgene expression were also discussed and have important future implications for evaluation of gene- and cell-based therapies for the failing heart. The current role of metabolic and receptor imaging was also briefly reviewed, as these represent the beginning of our clinical application of molecular imaging within the cardiovascular system. Part II will summarize the available targeted imaging probes as well as specific future applications of molecular imaging for identification and evaluation of critical pathophysiological processes of the cardiovascular system.

Evaluation of neovessels in atherosclerotic plaques of rabbits using an albumin‐binding intravascular contrast agent and MRI

To test whether B-22956/1, a novel intravascular contrast agent with a high affinity to serum albumin (Bracco Imaging SpA.), allowed quantifying neovessel and macrophage density in atherosclerotic plaques of rabbits using MRI. A T1-weighted MRI of the aorta was acquired in 10 rabbits (7 atherosclerotic and 3 control rabbits) before and up to 2 h after intravenous injection of 100 mumol/kg of Gd-DTPA or 75 mumol/kg of B-22956/1. Plaque enhancement was measured at different time points. Immunohistochemistry was performed using anti-CD 31 antibodies and anti-RAM 11 antibodies to correlate to neovessel and macrophage density, respectively. MRI showed a significant plaque enhancement 2 h after B-22956/1 versus Gd-DTPA in the atherosclerotic group (39.75% versus 9.5%; P < 0.0001. Early atherosclerotic plaques (n = 146) enhancement positively correlates with neovessel density on corresponding histological sections (r = 0.42; P < 0.01). Enhancement of atherosclerotic plaques 2 h after injection of B-22956/1 correlated with macrophage density (r = 0.71; P < 0.01). Enhancement of atherosclerotic plaques with MRI correlated with neovessel density at early time points after the injection of B-22956/1 and with macrophage density, at later time points. Hence, B-22956/1-enhanced MRI represents a promising imaging technique for the identification of "high-risk" plaques.

Detection of Neovessels in Atherosclerotic Plaques of Rabbits Using Dynamic Contrast Enhanced MRI and 18F-FDG PET

The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis. Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by DCE-MRI (r=0.89, P=0.016) and (2) 18F-FDG uptake evaluated by PET (r=0.5, P=0.103 after clustered robust, Huber-White, standard errors analysis). DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti-angiogenic therapies.

Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography

Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.

Effects of simvastatin on NF-κB-DNA binding activity and monocyte chemoattractant protein-1 expression in a rabbit model of atherosclerosis

To observe the effects of simvastatin on nuclear factor kappaB (NF-kappaB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), high-cholesterol group (HC), high-cholesterol+simvastatin group (HC+S) and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shiftassay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kappaB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kappaB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC+S groups were significantly lower than those in the HC group (P<0.05). There was no significant difference in the serum lipids between the LC and HC+S groups (P>0.05), but the NF-kappaB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC+S group were significantly decreased as compared to the LC group (P<0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kappaB-DNA binding activity and by reducing the expression of MCP-1 protein.

Antibody against cholesteryl ester transfer protein (CETP) elicited by a recombinant chimeric enzyme vaccine attenuated atherosclerosis in a rabbit model

The recombinant chimeric enzyme of AnsB-TTP-CETPC, which comprised asparagianse, tetanus toxin helper T-cell epitope and CETP B-cell epitope, was used to vaccinate New Zealand white rabbits in alum adjuvant. After anti-CETP antibodies were successfully produced, rabbits were fed with a high cholesterol diet for fifteen weeks until atherosclerotic lesions formed in arteries. The results showed that after CETP was inhibited by anti-CETP antibodies the fraction of plasma cholesterol in HDL increased and the fraction of plasma cholesterol in LDL decreased in rAnsB-TTP-CETPC immunized rabbits. The average size of aorta atherosclerotic plaques in rabbits treated with rAnsB-TTP-CETPC was 42.3% less than in rabbits treated with OVA (neutral control), or 47.6% less than in rabbits treated with rHSP65 (negative control). The average thickness of hyperplastic coronary artery in rAnsB-TTP-CETPC immunized rabbits was 159 ± 12 μm, which was significantly lower than in rHSP65 immunized rabbits (187 ± 15 μm) or OVA immunized rabbits (248 ± 18 μm). The data reported here demonstrated that rAnsB-TTP-CETPC could significantly attenuate the development of atherosclerosis in rabbits fed with high cholesterol diet, and might be developed to an anti-atherosclerosis vaccine in the future.

Systemic Response to Ambient Particulate Matter: Relevance to Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a risk factor for development of cardiovascular events, independent of smoking. The mechanisms are unclear, but systemic inflammation associated with COPD may contribute to this cardiovascular risk. Similar to cigarette smoking, exposure to particulate air pollution is associated with an increase in the mortality and morbidity from respiratory and cardiovascular diseases. The exposure of humans to high levels of ambient particles stimulates the bone marrow and the release of neutrophils, band cells, and monocytes into the circulation. This bone marrow simulation is associated with increased levels of circulating interleukin-1beta and interleukin-6, similar to cigarette smoking. In animals, exposure to particulate matter accelerates the transit of neutrophils and monocytes in bone marrow and expands the leukocyte pool size. This systemic inflammatory response to particle inhalation causes endothelial activation and upregulation adhesion molecules that are critically important in leukocyte recruitment into atherosclerotic plaques. Exposure to particles also causes disease progression and destabilization of atherosclerotic plaques in rabbits that develop atherosclerosis naturally. We suspect, therefore, that the systemic inflammatory responses described activate vascular endothelium and cause progression and instability of atherosclerotic plaques. We speculate that this mechanism may contribute to the cardiovascular morbidity and mortality associated with COPD.

Effects of Atherosclerotic Plaque on the Enlargement of an Experimental Model of Abdominal Aortic Aneurysm in Rabbits

Purpose. Abdominal aortic aneurysm (AAA) usually is associated with atherosclerosis. We attempted to create an abdominal aortic aneurysm with atherosclerotic plaque in rabbits to investigate the relationship between atherosclerosis and enlargement of AAA.Methods. An isolated segment of rabbit abdominal aorta was perfused with pancreatic elastase. Animals were fed a cholesterol-enriched diet to induce atherosclerotic plaque formation. Eight animals received perfusion with elastase and were fed a cholesterol-enriched diet (group EC), eight animals received perfusion with elastase and were fed a normal diet (group EN), eight animals received perfusion with saline and were fed a cholesterol-enriched diet (group SC), and eight animals received perfusion with saline and were fed a normal diet (group SN). Four animals served as a sham group. Each animal was killed after aortography at 4 or 12 weeks. The perfused segment was excised and examined histologically.Results. No animal treated with saline and fed normal diet (groups SN) developed either an aneurysm or atherosclerosis. Atherosclerotic plaque was observed in animals fed the cholesterol-enriched diet (groups SC and EC) at 4 weeks, and the plaque had thickened further by 12 weeks. All animals treated with elastase (groups EN and EC) developed an AAA. Maximum internal diameter in groups EN and EC (4.1 mm) was equal at 4 weeks, but at 12 weeks, the diameter was less for group EC than for group EN (4.0 mm versus 4.8 mm, P<0.05).Conclusion. Cholesterol-enriched diet following the intra-luminal perfusion of an isolated aortic segment with elastase produced an AAA with atherosclerotic plaque in rabbits. It is likely that the thickened intima with atheroma suppressed continued enlargement of the aneurysm in this model.

Experimental Thrombosis I: Relation with Fibrinogen and other Haemostatic Parameters ☆

Epidemiological studies have shown that the haemostatic parameters Fibrinogen (Fg), Factor VII (F VII), Factor VIII (F VIII), von Willebrand factor (vWF), Tissue Plasminogen Activator (t-PA), Plasminogen Activator Inhibitors (PAI) are risk factors/markers of ischemic cardiovascular disease. Ferritin (sFER) and Leukocytosis have also been implicated. In the present study we have followed the levels of fibrinogen, von Willebrand factor and thrombomodulin in relation to lipids, iron and the appearance of atherosclerotic lesions in New Zealand rabbits fed with a cholesterol enriched diet for a two-month period compared with a group of control rabbits. Hematocrit and white blood cell count (WBC) were measured in parallel. In hyperchlesterolemic rabbits the levels of fibrinogen and von Willebrand factor increased progressively, showing a positive correlation with the increasing cholesterol levels. There was an increase in soluble thrombomodulin beginning at the eighth week of study. In addition, these animals showed gross intimal atherosclerotic lesions in the whole extension of their aortas. Immunohistochemical studies showed the presence of fibrin(ogen) related antigen throughout the arterial wall and in the central portions of the atheromas. In the control group there was no formation of atherosclerotic plaques and all haemostatic, haematological and biochemical parameters were within the normal range. WBC and sFER levels were unaffected in both groups. Our results show that increased levels of fibrinogen and von Willebrand factor, known coronary risk factors, are strongly associated with the formation of atherosclerotic plaques in rabbits. The plaques contain a considerable amount of fibrinogen related antigen.

Vitamin E and factors affecting atherosclerosis in rabbits fed a cholesterol-rich diet

The present study aims to examine the effects of a palm-oil-derived vitamin E mixture containing tocotrienol (~70%) and tocopherol (~30%) on plasma lipids and on the formation of atherosclerotic plaques in rabbits given a 2% cholesterol diet. Eighteen New Zealand White rabbits (2.2-2.8 kg) were divided into three groups; group 1 (control) was fed a normal diet, group 2 (AT) was fed a 2% cholesterol diet and group 3 (PV) was fed a 2% cholesterol diet with oral palm vitamin E (60 mg/kg body weight) given daily for 10 weeks. There were no differences in the total cholesterol and triacylglycerol levels between the AT and PV groups. The PV group had a significantly higher concentrations of HDL-c and a lower TC/HDL-c ratio compared to the AT group (P < 0.003). The aortic tissue content of cholesterol and atherosclerotic lesions were comparable in both the AT and PV groups. However, the PV group had a lower content of plasma and aortic tissue malondialdehyde (P < 0.005). Our findings suggest that despite a highly atherogenic diet, palm vitamin E improved some important plasma lipid parameters, reduced lipid peroxidation but did not have an effect on the atherosclerotic plaque formation.

Vitamin E and factors affecting atherosclerosis in rabbits fed a cholesterol-rich diet

The present study aims to examine the effects of a palm-oil-derived vitamin Emixture containing tocotrienol (˜70%) and tocopherol (˜30%) on plasma lipids andon the formation of atherosclerotic plaques in rabbits given a 2% cholesterol diet.Eighteen New Zealand White rabbits (2.2–2.8 kg) were divided into three groups;group 1 (control) was fed a normal diet, group 2 (AT) was fed a 2% cholesterol dietand group 3 (PV) was fed a 2% cholesterol diet with oral palm vitamin E (60mg/kgbody weight) given daily for 10 weeks. There were no differences in the totalcholesterol and triacylglycerol levels between the AT and PV groups. The PV grouphad a significantly higher concentrations of HDL-c and a lower TC/HDL-c ratiocompared to the AT group (P < 0.003). The aortic tissue content of cholesterol andatherosclerotic lesions were comparable in both the AT and PV groups. However,the PV group had a lower content of plasma and aortic tissue malondialdehyde (P< 0.005). Our findings suggest that despite a highly atherogenic diet, palm vitaminE improved some important plasma lipid parameters, reduced lipid peroxidation butdid not have an effect on the atherosclerotic plaque formation.

MRI and NMR spectroscopy of the lipids of atherosclerotic plaque in rabbits and humans.

The early stages of atherosclerosis are characterized by the deposition of cholesteryl esters and triglycerides into the arterial wall. In the excised human atherosclerotic plaque these lipids are in a liquid-like state at body temperature and observable via MRI and NMR spectroscopy. To assess the ability of MRI to quantitatively image the lipids of atherosclerotic plaque in vivo, we have investigated eight New Zealand White rabbits fed atherogenic diets (2 weight (wt)% cholesterol, 1 wt% cholesterol + 6 wt% peanut oil, and 1 wt% cholesterol + 6 wt% com oil). Postmortem examination indicated that all rabbits developed atherosclerosis in the aorta. Except for one animal, magnetic resonance angiography showed no noticeable obstruction in the aorta. MRI was carried out in an attempt to image atherosclerotic plaque lipids directly, but no signal was detected in vivo. However, a plaque lipid signal was observed from excised tissue using a small diameter RF coil. 1H NMR spectroscopy of the atherosclerotic plaque from excised aortas indicated that the major fraction of plaque lipids in rabbits is not in a liquid state at physiological temperature and are only marginally MRI-visible compared to human plaque lipid. The differences in the MRI characteristics of rabbit and human plaque are due to differences in the fatty acid profile of the cholesteryl esters, chiefly a decrease of linoleic acid in rabbit lesions.

Dehydroepiandrosterone, dehydroepiandrosterone sulphate and cardiovascular disease.

High dehyroepiandrosterone (DHEA) or dehydroepiandrosterone sulphate (DHEAS) levels have been suggested to be protective for cardiovascular disease. DHEA supplementation is reported to lower low-density levels of cholesterol in humans and to reduce atherosclerotic plaques in rabbits. Several prospective studies have examined the relationship between DHEAS levels and cardiovascular disease but results have been conflicting. In men, estimated relative risks associated with one standard deviation increase in DHEAS levels range between 0.63 for coronary heart disease mortality in the Rancho Bernardo Study, 0.45 for fatal coronary heart disease but 1.11 for non-fatal coronary heart disease in the Honolulu Heart Study, 0.90 for myocardial infarction in the US Male Physicians study, and 1.34 in the Helsinki Heart Study. The only prospective study reporting data in women, the Rancho Bernardo Study, found DHEAS levels were not significantly associated with cardiovascular mortality. Variability in findings between studies may reflect the different endpoints used (DHEAS may influence mortality but not incidence), or may indicate a more complex relationship between DHEAS and other biological processes directly causally related to cardiovascular disease, which may vary in different age and sex groups. Cigarette smoking may be an important confounder since it increases cardiovascular disease risk but is also associated with increased DHEAS levels. It is notable that populations which have the lowest coronary heart disease rates and greatest longevity such as the Japanese also reportedly have low mean DHEAS levels, so DHEAS per se does not appear to explain between-population differences in cardiovascular incidence or longevity. Intervention studies in humans to examine the effect of pharmacological or physiological doses of DHEA on biological variables such as lipid levels, glucose tolerance and insulin sensitivity have been limited in size and duration and results have been inconsistent. While the data to date are intriguing, the clinical significance of DHEA and DHEAS in cardiovascular disease remains uncertain. There is still a lack of understanding of the basic biological effects of DHEA and DHEAS and further data both in men and in women from prospective studies and randomized trials are urgently needed.

Preferential uptake of a water-soluble phthalocyanine by atherosclerotic plaques in rabbits

This study is the first demonstration of preferential accumulation of a water soluble phthalocyanine dye in atheromatous plaques in the rabbit. Two groups of rabbits with diet-induced atheromatous plaques were killed 4 and 24 h following intravenous administration of copper phthalocyanine tetrasulfonate. Uptake of the dye by plaque-containing and normal appearing aortae was evaluated macroscopically and quantitatively by extraction of the dye from the tissues. The concentration of the dye in the atheromatous plaques was 2.6 and 1.7 times higher than in the normal vessel wall at 4 and 24 h, respectively. The concentration of the dye in normal appearing aortae in the 2 study groups was similar to that of aortae of control rabbits which were fed a normal diet and exposed to the dye for the same time periods. We conclude that copper phthalocyanine accumulates preferentially in atheromatous plaques in rabbits. These findings provide a basis for the utilization of phthalocyanines for plaque identification and for photodynamic therapy of atherosclerosis.

The Effects of Heparin Upon Atherogenesis in the Watanabe Heritable Hyperlipidemic Rabbit

Heparin is routinely added to vascular cell cultures to inhibit smooth muscle cell proliferation. The in vivo effects of heparin upon atherogenesis have remained controversial, however. In this experiment 13 four-month-old, heritably hyperlipidemic, Watanabe rabbits were randomly assigned to three treatment groups: 1500 U heparin, 500 U heparin, or saline. An injection protocol was followed for nine months. The rabbits were bled monthly from their marginal ear veins and plasma from these bleeds was analyzed for cholesterol and triglyceride content. At sacrifice each rabbit's aorta was sampled at 10 specific locations from the arch to the iliac bifurcation. The reduction in the area of the aorta by atherosclerotic plaque at each site was calculated using a video imaging system. Heparin injections significantly reduced mean plasma levels of cholesterol and triglycerides compared to pretreatment levels and saline injected controls. However, the magnitude of the reduction was not dose-related. The aortic luminal area occupied by atherosclerotic plaque in rabbits injected with 1500 U of heparin was significantly less (p less than .05) than in rabbits injected with saline or 500 U of heparin. Plaques from heparin-treated animals contained more fatty deposits and foam cells compared to the plaques from saline-treated rabbits which were more fibromuscular in organization. We conclude that heparin modulates the occurrence and composition of atherosclerotic plaques in this animal model of naturally occurring atherogenesis.

Drag-reducing polymers: A novel class of diuretic and natriuretic compounds

Previous studies have demonstrated that Separan AP-30, a drag-reducing polymer, significantly decreased the formation of atherosclerotic plaques in rabbits fed a high-cholesterol diet. Furthermore, Separan AP-273, a polymer similar to but longer than Separan AP-30, markedly increased cardiac output in open-chest rats. Preliminary studies in our laboratory have described diuresis and natriuresis following the intravenous infusion of Separan AP-273. These studies did not determine whether this natriuresis was common to drag-reducing polymers or unique to Separan. In the present study the renal effects of two chemically dissimilar drag-reducing polymers of molecular lengths approaching approximately 100 microns were compared. Sprague-Dawley rats (250-300 g) were anesthetized (Nembutal) and a tracheostomy was performed. A baseline level of sodium and water excretion was established by the infusion of saline (0.097 ml/min, IV). Separan (0.004%), an anionic polyacrylamide; Polyox (0.4%), a poly(ethylene oxide); or mannitol (20%), an osmotic diuretic, was infused into the jugular vein at 0.0034 ml/min. Separan and Polyox both increased the excretion of sodium and water (p less than 0.05). At the doses tested, potassium excretion was unaltered in both groups. Separan, but not Polyox, produced a modest increase in blood pressure. Creatinine clearance was unaltered. At this infusion rate, only hypertonic concentrations of mannitol (20%) induced a similar effect. These results indicate that drag-reducing polymers may represent a novel class of potassium-sparing diuretic and natriuretic compounds. The ability of this class of polymers to decrease the formation of atherosclerotic plaques, increase blood flow, and produce a potassium-sparing natriuresis may be of practical clinical significance.

Scintigraphic detection of atherosclerotic plaques in rabbits with 111In-labeled hematoporphyrin derivative

The efficacy of 111In-labeled hematoporphyrin derivative (HPD) in localizing and detecting atheromas had been investigated with 10 atherogenic New Zealand white rabbits. Atherosclerotic plaques surgically induced in the abdominal aorta showed selective uptake of 111In-HPD over normal blood vessels averaging 0.01% ID/g tissue (range 0.003–0.023% ID/g). Normal aorta and thoracic artery concentrated an average of 0.0026% ID/g which is less than the mean blood activity of 0.0034% ID/mL. Statistical analysis demonstrated significant difference in the uptake of 111In-HPD by the atherosclerotic plaque segments as compared to normal abdominal aorta ( P = 0.0023) and normal thoracic artery ( P = 0.0012). In hypercholesteremic rabbits, the mean plaque segment to normal blood vessels ratio was 4:1 (range 2 to 9:1) sufficiently high to permit plaque delineation in the scintigram. Although 111In-HPD showed promise as a plaque imaging agent, further investigation with large animal models such as primates is needed to confirm current findings.

The effect of chromium on established atherosclerotic plaques in rabbits

Twenty-three rabbits were fed for 8 weeks with standard diet to which was added a 1.5% cholesterol supplement. After this the cholesterol supplement was discontinued, but 11 rabbits received a daily intraperitoneal injection of 20 micrograms of potassium chromate while the remaining 12 received distilled water. The aortas were examined after a further 30 weeks; their mean weight per unit length was 1.27 g (SE +/- 0.17) in the control group and 0.81 g (SE +/- 0.08) in the chromium treated group (t = 2.36; P < 0.05). The percentage area of intimal surface covered by plaques was 94.8% (SE +/- 1.7) and 62.6% (SE +/- 10.4), respectively (t = 3.53; P < 0.005), and the total cholesterol content per unit length of aorta was 729 mg/100 ml (SE +/- 44.0) and 457.8 mg/100 ml (SE +/- 117.1), respectively (t = 23; P < 0.05). The results show a significant effect of chromium on the regression of cholesterol-induced atherosclerotic plaques in rabbits.

A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.