Atherosclerotic Plaque Components Research Articles

Some Biochemical Alternations Associated with Oral Contraceptives And Atherosclerosis in Albino Rats.

An excess intake of vitamin D2 can result in mobilization of calcium in the skeleton and increase the serum calcium level. This calcium is taken up by soft tissues such as arteries. The risk of calcium builds up in arteries, a significant component of atherosclerotic plaque. Many researches clarify the relationship between oral contraceptives and atherosclerosis. This study aims to evaluate the changes in some biochemical parameters as well as the histopathological examination of liver and aorta following the administration of hormonal oral contraceptives (O .CS) with different concentrations of estrogen (ethinyle-estradiol) (E.E) and progestogen DL-norgestrel (norethindrone) (NOR.) to the atherosclerotic rats. In addition to this, the study clarifies the role of low dose oral contraceptives. 48 adult female albino rats were divided into six comparable groups of 8 animals each. Group I (Gr.1) was considered as control, group II (Gr. II) was intramuscularly (i.m.) injected with vit. D2 350.000 IU /kg B.W., group III (Gr. III) administered O.C (35 g E.E/0.5 mg NOR.), group IV (Gr. IV) received (vit. D2 350.000 I.U vit. D2 /kg B.W plus O.C 35 g E.E/0.5 mg.), group V(Gr.V) received (vit. D2 350.000 I.U/kg B.W. plus O.C 35 g E.E/1mg NOR.), group VI (Gr.VI) received (vit. D2350.000 I.U /kg B.W.plus O.C 70 g E.E/0.5 mg NOR.) daily for an experimental period eight weeks.Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum alkaline phosphatase (ALP) displayed significant increase in the following groups (higher progestogen concentrations in O.Cs plus vit. D2 treated group, at low-dose O.C plus vit. D2 treated group, at higher estrogen dose within O.C plus vit. D2 treated group, vit. D2 treated,and at low-dose O.C treated group). Serum triglycerides recorded significant increase in group treated with higher estrogen dose within O.C plus vit. D2 treated group, low-dose O.C plus vit. D2 treated group , higher progestogen concentrations in O.Cs plus vit. D2 treated group, vit. D2 treated group,and at low-dose O.C treated group respectively. Serum total cholesterol increased significantly in higher progestogen concentrations in O.Cs plus vit. D2 treated group, at low-dose O.C plus vit. D2 treated group, vit. D2 treated group, low-dose O.C treated group and at higher estrogen dose within O.C plus vit. D2 treated group at 8 weeks in comparison with control. Histopathological studies of livers showed severe at the higher progestogen concentration in O.C plus vit. D2 treated group and at low dose O.C plus vit. D2 treated group .Liver displayed moderate degenerative changes in higher estrogen dose within O.C plus vit. D2 treated group, in vit. D2 treated group and in low dose O.C treated group. Media calcinosis in aorta was more obvious at the higher progestogen concentrations in O.Cs plus vit. D2 treated group. Also it develops at low dose O.C treated group. In conclusion atherosclerosis may develop at low dose O.C due to progestogen content.

Some Biochemical Alternations Associated with Oral Contraceptives And Atherosclerosis in Albino Rats.

An excess intake of vitamin D2 can result in mobilization of calcium in the skeleton and increase the serum calcium level. This calcium is taken up by soft tissues such as arteries. The risk of calcium builds up in arteries, a significant component of atherosclerotic plaque. Many researches clarify the relationship between oral contraceptives and atherosclerosis. This study aims to evaluate the changes in some biochemical parameters as well as the histopathological examination of liver and aorta following the administration of hormonal oral contraceptives (O .CS) with different concentrations of estrogen (ethinyle-estradiol) (E.E) and progestogen DL-norgestrel (norethindrone) (NOR.) to the atherosclerotic rats. In addition to this, the study clarifies the role of low dose oral contraceptives. 48 adult female albino rats were divided into six comparable groups of 8 animals each. Group I (Gr.1) was considered as control, group II (Gr. II) was intramuscularly (i.m.) injected with vit. D2 350.000 IU /kg B.W., group III (Gr. III) administered O.C (35 g E.E/0.5 mg NOR.), group IV (Gr. IV) received (vit. D2 350.000 I.U vit. D2 /kg B.W plus O.C 35 g E.E/0.5 mg.), group V(Gr.V) received (vit. D2 350.000 I.U/kg B.W. plus O.C 35 g E.E/1mg NOR.), group VI (Gr.VI) received (vit. D2350.000 I.U /kg B.W.plus O.C 70 g E.E/0.5 mg NOR.) daily for an experimental period eight weeks.Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum alkaline phosphatase (ALP) displayed significant increase in the following groups (higher progestogen concentrations in O.Cs plus vit. D2 treated group, at low-dose O.C plus vit. D2 treated group, at higher estrogen dose within O.C plus vit. D2 treated group, vit. D2 treated,and at low-dose O.C treated group). Serum triglycerides recorded significant increase in group treated with higher estrogen dose within O.C plus vit. D2 treated group, low-dose O.C plus vit. D2 treated group , higher progestogen concentrations in O.Cs plus vit. D2 treated group, vit. D2 treated group,and at low-dose O.C treated group respectively. Serum total cholesterol increased significantly in higher progestogen concentrations in O.Cs plus vit. D2 treated group, at low-dose O.C plus vit. D2 treated group, vit. D2 treated group, low-dose O.C treated group and at higher estrogen dose within O.C plus vit. D2 treated group at 8 weeks in comparison with control. Histopathological studies of livers showed severe at the higher progestogen concentration in O.C plus vit. D2 treated group and at low dose O.C plus vit. D2 treated group .Liver displayed moderate degenerative changes in higher estrogen dose within O.C plus vit. D2 treated group, in vit. D2 treated group and in low dose O.C treated group. Media calcinosis in aorta was more obvious at the higher progestogen concentrations in O.Cs plus vit. D2 treated group. Also it develops at low dose O.C treated group. In conclusion atherosclerosis may develop at low dose O.C due to progestogen content.

Generation of C-Reactive Protein and Complement Components in Atherosclerotic Plaques

C-reactive protein (CRP) and complement are hypothesized to be major mediators of inflammation in atherosclerotic plaques. We used the reverse transcriptase-polymerase chain reaction technique to detect the mRNAs for CRP and the classical complement components C1 to C9 in both normal arterial and plaque tissue, establishing that they can be endogenously generated by arteries. When the CRP mRNA levels of plaque tissue, normal artery, and liver were compared in the same cases, plaque levels were 10.2-fold higher than normal artery and 7.2-fold higher than liver. By Western blotting, we showed that the protein levels of CRP and complement proteins were also up-regulated in plaque tissue and that there was full activation of the classical complement pathway. By in situ hybridization, we detected intense signals for CRP and C4 mRNAs in smooth muscle-like cells and macrophages in the thickened intima of plaques. By immunohistochemistry we showed co-localization of CRP and the membrane attack complex of complement. We also detected up-regulation in plaque tissue of the mRNAs for the macrophage markers CD11b and HLA-DR, as well as their protein products. We showed by immunohistochemistry macrophage infiltration of plaque tissue. Because CRP is a complement activator, and activated complement attacks cells in plaque tissue, these data provide evidence of a self-sustaining autotoxic mechanism operating within the plaques as a precursor to thrombotic events.

Attenuation of hypothermia-induced platelet activation and platelet adhesion to artificial surfaces in vitro by modification of hemoglobin to carry S-nitric oxide and polyethylene glycol

Hypothermic cardiopulmonary bypass alters platelet function and hypothermia is associated with postoperative myocardial ischemia. Thrombogenic surfaces such as extracorporeal circuits, vascular graft materials, and components of atherosclerotic plaque induce activation of platelets. The effects of human hemoglobin (Hb) covalently modified to carry S-nitric oxide (NO) functional groups (SNO-Hb), polyethylene glycol (PEG-Hb), and SNO–PEG-Hb on platelet activation were studied. Platelet activation was assessed by cytometric analysis of GPIIb–IIIa activation and P-selectin expression at hypothermic condition (22°C) after stimulation with Hb derivatives. Platelet adhesion and aggregation were measured in a parallel glass plate chamber coated with unmodified Hb, SNO-Hb, PEG-Hb, SNO–PEG-Hb, and collagen. Platelet binding of antibodies to GPIIb–IIIa and P-selectin was significantly enhanced by hypothermic condition and by unmodified Hb. There was significantly less platelet binding of antibodies to GPIIb–IIIa and P-selectin with SNO-Hb, PEG-Hb, and SNO–PEG-Hb compared with unmodified Hb. There was significantly less platelet attachment, adhesion, and aggregation on the SNO-Hb, PEG-Hb and SNO–PEG-Hb coated surfaces compared with unmodified Hb-coated and -uncoated surfaces. SNO-Hb, PEG-Hb, and SNO–PEG-Hb induced less platelet activation at hypothermic temperature, and induced less platelet adhesion and aggregation on thrombogenic surfaces compared with unmodified Hb. The inhibitory effect may be derived from antiadhesive properties of Hb, antiplatelet actions of NO, and molecular barrier action of PEG.

In vivo quantification of atherosclerotic plaque components with MRI in a rabbit model of atherosclerosis

In vivo quantification of atherosclerotic plaque components with MRI in a rabbit model of atherosclerosis

The Carboxyl-Terminal Fragment of α1-Antitrypsin Is Present in Atherosclerotic Plaques and Regulates Inflammatory Transcription Factors in Primary Human Monocytes

α1-Antitrypsin (AAT) serine proteinase inhibitor is found in most biological fluids, diffuses into most tissues, and is an important factor in controlling tissue damage by proteases in inflammatory diseases such as atherosclerosis. We have previously reported that the C-terminal fragment (C-36) generated during the cleavage of AAT by proteinases forms amyloid fibrils which have biological effects unrelated to precursor functions. Here we show that the C-36 fragment is present in atherosclerotic plaques, particularly within the fibrous cap at the base of the lipid core. We also found that human monocyte stimulation with C-36 fibrils led to a strong activation of both peroxisome proliferator-activated receptors α and γ (PPARα and PPARγ) at 1, 2, and 18 h of cell culture. A parallel increase in the intracellular lipid accumulation was also observed. Furthermore, stimulation of monocytes with C-36 for 18 h led to activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) activation. These data for the first time demonstrate the peptide of AAT as a component of atherosclerotic plaques and as a novel activator of PPARα, PPARγ, NF-κB, and AP-1 in cultured monocytes. Taken together, the effects of the peptide represent a new mechanism of monocyte activation that may be of importance not only in atherogenesis, but also in other inflammatory processes.

Characterization of signal properties in atherosclerotic plaque components by intravascular MRI.

Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid endarterectomy specimens with the use of a 5F catheter-based imaging coil, standard acquisition software, and a clinical scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37 degrees C by use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T General Electric interventional scanner. Cross-sectional intravascular MRI (156x250 microm in-plane resolution) that used different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio, the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional signal loss in gradient echo (gradient echo-to-spin echo ratio) in plaque components. Histological staining included hematoxylin and eosin, Masson's trichrome, Kossa, oil red O, and Gomori's iron stain. X-ray micrographs were also used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was significantly less in the fibrous cap (0.62+/-13) than in all other components (P<0.05) The inversion ratio was greater in lipid (0.91+/-0.09) than all other components (P<0.05). Calcium was best distinguished by using the gradient echo-to-spin echo ratio, which was lower in calcium (0.36+/-0.2) than in all plaque components, except for the organizing thrombus (P<0.04). Absolute T1 (range 300+/-140 ms for lipid to 630+/-321 ms for calcium) and T2 (range 40+/-12 ms for fresh thrombus to 59+/-21 ms for smooth muscle cells) were not significantly different between groups. In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to visualize major plaque components. Pulse sequences that take advantage of differences in biochemical structure of individual plaque components show quantitative differences in signal properties between fibrous cap, lipid, and calcium. Therefore, catheter-based imaging coils may have the potential to identify and characterize those intraplaque components associated with plaque stability by use of existing whole-body scanners.

The diagnostic accuracy of ex vivo MRI for human atherosclerotic plaque characterization.

Recent evidence indicates that the type of atherosclerotic plaque, rather than the degree of obstruction to flow, is an important determinant of the risk of cardiovascular complications. In previous work, the feasibility of using MRI for the characterization of plaque components was shown. This study extends the previous work to all the plaque components and shows the accuracy of this method. Twenty-two human carotid endarterectomy specimens underwent ex vivo MRI and histopathological examination. Sixty-six cross sections were matched between MRI and histopathology. In each cross section, the presence or absence of plaque components were prospectively identified on the MRI images. The overall sensitivity and specificity for each tissue component were very high. Calcification and fibrocellular tissue were readily identified. Lipid core was also identifiable. However, thrombus was the plaque component for which MRI had the lowest sensitivity. A semiautomated algorithm was created to identify all major atherosclerotic plaque components. MRI can characterize carotid artery plaques with a high level of sensitivity and specificity. Application of these results in the clinical setting may be feasible in the near future.

Reverse Cholesterol Transport and Atherosclerosis Regression

Cholesterol is the major component of atherosclerotic plaque. Cholesterol accumulation within atherosclerotic plaque occurs when cholesterol influx into the arterial wall (from apoB-containing lipoproteins) exceeds cholesterol efflux. Increased influx of cholesterol into the arterial wall is accompanied by an increased influx of monocytes/macrophages,1 which take up oxidized and aggregated LDL and store the cholesterol as esters. Whereas parenchymal cells maintain cholesterol balance by downregulating de novo cholesterol synthesis and LDL receptor expression, macrophages continue to take up cholesterol from apoB-containing lipoproteins via pathways that are not subject to sterol-mediated feedback control. Current strategies to reduce coronary heart disease (CHD) are aimed primarily at reducing the influx of cholesterol into the arterial wall by lowering plasma LDL cholesterol concentrations. Aggressive lowering of plasma LDL levels reduces mortality from CHD,2 but protection is not complete, and in a significant proportion of patients, plasma LDL concentrations cannot be lowered to a level that would be predicted to halt the progression of disease. As a consequence, there is great interest in strategies aimed at enhancing cholesterol efflux from the arterial wall and promoting its transport to the liver for excretion. Cholesterol that is synthesized in extrahepatic tissues or acquired from lipoproteins is returned to the liver for excretion in a process called reverse cholesterol transport.3 The initial step in reverse cholesterol transport is thought to be efflux of cholesterol from cell membranes to acceptor particles in the interstitial fluid. Two models have been proposed with regard to the movement of cholesterol from plasma membrane to acceptor particles. In the first, the aqueous diffusion model, cholesterol molecules spontaneously desorb from cell membranes and are then incorporated into acceptor particles after traversing the intervening aqueous space by diffusion.4 Phospholipid vesicles, phospholipid/albumin complexes, and triglyceride/phospholipid emulsions efficiently remove cholesterol from cells via this …

LDL particle size: an important drug target?

Low density lipoprotein (LDL) is the main carrier of plasma cholesterol and a major component of atherosclerotic plaque [1]. Lowering LDL cholesterol reduces coronary events and mortality from coronary artery disease (CAD) [2–4], however, the relation between LDL cholesterol concentration and (CAD) is complex. Many patients with CAD have plasma LDL cholesterol concentrations in the normal rangefor the general population [5]. Thus, it could be that coronary risk goes beyond LDL cholesterol concentration to the characteristics of the LDL particles themselves. The purpose of this communication is to address the issue of whether LDL particle size and density influences its atherogenecity and how this might be modified by drug therapy.

In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement

OBJECTIVESThe purpose of this study was to target acoustically reflective liposomes to atherosclerotic plaques in vivo for ultrasound image enhancement.BACKGROUNDWe have previously demonstrated the development of acoustically reflective liposomes that can be conjugated for site-specific acoustic enhancement. This study evaluates the ability of liposomes coupled to antibodies specific for different components of atherosclerotic plaques and thrombi to target and enhance ultrasonic images in vivo.METHODSLiposomes were prepared with phospholipids and cholesterol using a dehydration/rehydration method. Antibodies were thiolated for liposome conjugation with N-succinimidyl 3-(2-pyridyldithio) propionate resulting in a thioether linkage between the protein and the phospholipid. Liposomes were conjugated to antifibrinogen or anti–intercellular adhesion molecule-1 (anti–ICAM-1). In a Yucatan miniswine model, atherosclerosis was developed by crush injury of one carotid and one femoral artery and ingestion of a hypercholesterolemic diet. After full plaque development the arteries were imaged (20-MHz intravascular ultrasound catheter and 7.5-MHz transvascular linear probe) after injection of saline, unconjugated liposomes and antibody conjugated liposomes.RESULTSConjugated liposomes retained their acoustically reflective properties and provided ultrasonic image enhancement of their targeted structures. Liposomes conjugated to antifibrinogen attached to thrombi and fibrous portions of the atheroma, whereas liposomes conjugated to anti–ICAM-1 attached to early atheroma.CONCLUSIONSOur data demonstrate that this novel acoustic agent can provide varying targeting with different antibodies with retention of intravascular and transvascular acoustic properties.

Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells

Background. Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab') 2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques. Methods. The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 μg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48 , and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining. Results. Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed. Conclusion. This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.

Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses.

Increasing the contrast between atheromatous plaque components is a major issue in cardiovascular MRI research. It would allow one to identify unstable plaque by differentiating the lipid core associated with vulnerability, from the fibrous cap, considered as a factor of stability. T2 and diffusion-weighted imaging have already provided satisfying results. Magnetization transfer (MT) between restricted protons Hr and free-water protons Hf could achieve a different contrast related to collagen and lipoprotein macromolecules present in the fibrous cap and lipid core, respectively. The purpose of this work was to evaluate in vitro the MT effect produced by adapted T2-selective 1-3-3-1 binomial pulses on isolated samples of atheromatous arteries at 3 T. A method based on simulation was used in order to improve the MT specificity: it is shown that 50% 1-3-3-1 pulses (the percentage indicating the level of Hr saturation) allow an estimation of T2r, the Hr T2. Using this technique, magnetization transfer was observed for the first time in atherosclerotic plaque components, an effect more pronounced for the fibrous cap and media than for the lipid core and adventitia. The T2r estimation gave values ranging from 20 to 25 micros for the four samples. This preliminary study provides a basis for establishing an MT imaging sequence of atheromatous arteries, by using 50% 1-3-3-1 pulses calibrated for saturating protons with a 20 micros T2. This MT protocol should be further compared to T2 and diffusion-weighted imaging.

Coronary atherosclerosis: is the process focal or diffuse among patients with symptomatic or fatal myocardial ischemia?

Coronary atherosclerosis among patients with symptomatic or fatal myocardial ischemia is a diffuse and extensive process, and it affects all 4 of the major (right, left main, left anterior descending, and left circumflex) epicardial arteries. Histologic evaluation of 5-mm arterial segments reveals involvement of the entire lengths of the epicardial arteries, although the size of plaque may vary from segment to segment. The dominant component of atherosclerotic plaque among patients with symptomatic or fatal myocardial ischemia is fibrous tissue.

Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses

Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses

Identification of Fibrillins as a Major Component of Coronary Atherosclerotic Plaques

Fibrillins are two distinct 350 kD RGD-containing glycoproteins found in microfibrils in the extracellular matrix. Fibrillin-containing microfibrils are required for elastic fiber formation and serve as an anchor for protein binding via β1 and/or αvβ3 receptors. Fibrillin-1 is causally linked to Marfan’s syndrome, which is in part characterized by disruption of the aortic media. Fibrillin-2 is causally linked to congenital contractural arachnodactyly, which is rarely characterized by cardiovascular symptoms. We hypothesized that fibrillins might be present in coronary atherosclerotic plaques and contribute to plaque stability. To test this, we examined the expression of fibrillins-1 and -2 in human coronary arteries and coronary atherectomies. Positive staining for fibrillin-1 and fibrillin-2 proteins was observed by immunochemistry in 95% of the specimens. Fibrillin-1 was localized to the plaque, adventitia, and endothelial cells. Fibrillin-2 stained diffusely in the adventitia and focally in the plaque. Neither fibrillin was abundant in the media. Substantial differences between the amount and localization of histologically stained elastic fibers and fibrillin immunohistochemical staining were noted. By in situ hybridization, fibrillin-1 mRNA was localized to smooth muscle cells, endothelial cells, and fibroblasts. In spite of the presence of fibrillin-2 antigen by immunohistochemistry, fibrillin-2 mRNA was not detected by in situ hybridization. These data implicate fibrillins as important components of the atherosclerotic plaque. Fibrillins may contribute to plaque stability and act as binding sites for other macromolecules within the atherosclerotic lesion.

Behavior of Atherosclerotic Plaque Components After in Vitro Angioplasty and Atherectomy Studied by High Field MR Imaging

Aims: Using magnetic resonance imaging (MRI), we developed in vitro models to image the response of fatty, fibrous, and calcified plaques to in vitro models of angioplasty and atherectomy, and tested the resistance of collagenous cap and lipid core to radial compression. Methods and Results: We studied the effects of balloon compression on 10 fibrous plaques with a complete collagenous cap (group A), 6 fatty plaques without cap (group B), and 5 calcified plaques (group C). Atherectomy was performed on nine other fibrous lesions (group D). In group A, fibrous cap, lipid core, and plaque did not change after radial compression despite a decrease in luminal obstruction due to medial stretching. In group B, a reduction of plaque (−30%) and lipid core (−35%) were observed. Compression dissected calcified plaques at the shoulder level. In group D, atherectomy reduced collagenous cap by 54%, and plaque by 35%. Conclusions: In these models, MRI shows 1) the high resistance of collagenous caps to radial compression, 2) a stretching effect of compression on disease-free walls, enlarging lumen in case of fibrous plaque, but a reduction and redistribution of lipid cores in case of fatty plaques, 3) the rupture of calcified arteries at the plaque shoulder, and 4) the reduction of fibrous components by atherectomy but not by angioplasty. By characterizing plaque composition, MRI may allow a predictable response of atherosclerotic arteries to interventional procedures.

Macrophage Scavenger Receptors and Atherosclerosis

A hallmark of atherosclerosis is the deposition of plasma cholesterol in atherosclerotic plaques in arterial walls. Key cellular components of atherosclerotic plaques are foam cells, which are derived from monocytes-macrophages. In order to elucidate the molecular mechanism of foam cell formation, we cloned and characterized cDNA for type I and II MSR. Type I and II MSR can bind an extraordinary wide range of ligands using its “charged collagen structure”, including modified low density lipoproteins (mLDL) and bacterial pathogens. MSR also mediates phagocytosis of apoptotic cells and cation-independent macrophage adhesion in vitro. Targeted disruption of type I and II MSR gene in mice results in a marked reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from type I and II MSR deficient mice show a marked decrease in mLDL degradation activity in vitro, whereas mLDL clearance from the plasma occurs at a normal rate. In addition, type I and II MSR-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type I, indicating that type I and II MSR may play a part in host defense against pathogens.

EFFECTS OF CORONARY ANGIOPLASTY ON MONOCYTE TISSUE FACTOR RESPONSE IN PATIENTS WITH STABLE OR UNSTABLE ANGINA

Balloon coronary angioplasty is a revascularization procedure which increases the luminal diameter at a site of arterial stenosis, leading to mechanical disruption of the atherosclerotic plaque and to stretching of the vascular wall (1). This procedure can be complicated by thrombosis or restenosis, which occur in 5% and 30% of the cases respectively (2). These complications probably result from exposure of blood to components of atherosclerotic plaque, subendothelium and components of vascular wall, leading to activation of coagulation (thrombin generation) and platelets (3,4). Recent data point to simultaneous increase of leukocyte adhesive receptors, indicating an additional process of leukocyte activation, which could play a key role in the vascular healing process after angioplasty (5). These elements could also play a role in the thrombotic and stenotic complications.

Dressing Up the Palmaz-Schatz Stent

We are approaching the 20th anniversary of the first use of coronary balloon angioplasty in humans. This nonsurgical treatment of obstructive coronary atherosclerosis has proved effective in relieving subjective and objective manifestations of myocardial ischemia, with recent clinical trials demonstrating comparability with coronary artery bypass surgery in selected patients with advanced multivessel disease (References 1 through 5 and personal observations). Despite impressive technical refinements of equipment and technique, balloon angioplasty continues to be plagued by three major limitations: (1) inability to treat certain types of coronary lesions, particularly those presenting as chronic total occlusion; (2) the potential of acutely aggravating coronary obstruction by means of coronary dissection, spasm, or thrombosis necessitating emergency coronary bypass surgery or causing myocardial infarction; and (3) recurrence of coronary narrowing 3 to 6 months after initial treatment. New devices have been developed in response to these shortcomings. Directional atherectomy can remove a component of the obstructive atherosclerotic plaque, but clinical superiority over conventional balloon angioplasty has been questioned.6 7 8 High-speed rotational atherectomy drills plaque and allows treatment of certain coronary narrowings that cannot be treated with a balloon catheter and appears to enhance the effectiveness and safety of conventional angioplasty for patients with complex lesions.9 10 11 Efforts are ongoing to determine whether debulking lesions alone or in conjunction with balloon angioplasty will reduce the chance of lesion recurrence.12 Devices such as direct laser angioplasty, laser-heated balloon angioplasty, and extraction atherectomy have been shown to be feasible techniques, but their marginal utility has been null or minimal. Coronary stents, percutaneously deployed metallic endovascular prostheses, have had a substantial impact on improving the immediate and late outcomes of patients treated with balloon angioplasty. The first evidence of efficacy was demonstrated by the Gianturco-Roubin stent that is based on a continuous-coil design. This …