Normal Rabbit Aorta Research Articles

L-Arginine reduces downstream vascular contractility after flow-diverting device deployment: A preliminary study in a rabbit model.

Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model. FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH. Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively). These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.

Downstream vascular changes after flow-diverting device deployment in a rabbit model

BackgroundFlow diverters (FDs) are increasingly used in the treatment of intracranial aneurysms, and carry the risk of thromboembolic complications, even in patients treated with dual antiplatelet therapy. The effect of...

Selective ablation of atherosclerotic lesions with less thermal damage by controlling the pulse structure of a quantum cascade laser in the 5.7-µm wavelength range

Cholesteryl esters are the main components of atherosclerotic plaques, and they have an absorption peak at the wavelength of 5.75 µm. To realize less-invasive ablation of the atherosclerotic plaques using a quasi-continuous wave (quasi-CW) quantum cascade laser (QCL), the thermal effects on normal vessels must be reduced. In this study, we attempted to reduce the thermal effects by controlling the pulse structure. The irradiation effects on rabbit atherosclerotic aortas using macro pulse irradiation (irradiation of pulses at intervals) and conventional quasi-CW irradiation were compared. The macro pulse width and the macro pulse interval were determined based on the thermal relaxation time of atherosclerotic and normal aortas in the oscillation wavelength of the QCL. The ablation depth increased and the coagulation width decreased using macro pulse irradiation. Moreover, difference in ablation depth between the atherosclerotic and normal rabbit aortas using macro pulse irradiation was confirmed. Therefore, the QCL in the 5.7-µm wavelength range with controlling the pulse structure was effective for less-invasive laser angioplasty.

Local pulse wave velocity directly reflects increased arterial stiffness in a restricted aortic region with progression of atherosclerotic lesions.

We investigated local pulse wave velocity (LPWV) in different aortic segments with respect to the rheological properties of the aorta with age-related progression of atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Normal and KHC rabbits aged 10-12, 22-24 and 34-36 months were anesthetized with pentobarbital sodium (30 mg kg(-1), intravenous). Pulse waves at the ascending aorta were recorded simultaneously with those at the proximal, middle and distal thoracic and abdominal aortas by moving a catheter with three micromanometers (40-mm intervals) at 80-mm intervals from the origin of the descending thoracic aorta. The aortic diameter was measured using an intravascular imaging system at the same aortic position at which the pulse waves were measured. LPWV was the greatest in the aortic arch, decreased gradually in the thoracic aorta and increased again in the abdominal aorta in KHC rabbits, whereas it was the lowest in the aortic arch, increased slightly in the thoracic aorta and increased gradually in the abdominal aorta in normal rabbits. LPWV increased significantly with age in most aortic segments. The change pattern of LPWV resembled that of the percent fractional lesioned area where LPWV was determined. The significant increase in LPWV with age was mainly due to the increase in the elastic modulus of the aortic wall with atherosclerotic progression as well as the increase in wall thickness. LPWV accurately detected the presence of atherosclerotic lesions and alteration in the rheological properties of the aortic regions through which pulse waves travelled.

Sonographic Assessment of Atherosclerotic and Hypercholesterolemic Artery Using the Echo-Tracking Technique in an Animal Model

The purpose of this study was to ascertain the utility of sonography with the echo-tracking (ET) technique to assess vascular stiffness in rabbits with hypercholesterolemia and atherosclerosis. Grayscale sonography associated with the ET technique was used to measure the elastic modulus (Ep) of the aorta in cholesterol-fed rabbits (group T1, n = 44, for 4 weeks; group T2, n = 44, for 12 weeks) and normal control rabbits (group C1, n = 44; group C2, n = 44). The aortic Ep values and blood biochemical markers between groups were compared using analysis of covariance. Light and transmission electron microscopic evaluation were used to demonstrate atherosclerotic changes in the aorta. The Ep values of the aorta in group T1 and T2 rabbits were significantly higher than those of group C1 and C2 controls (88.74 +/- 27.99 and 100.96 +/- 24.81 vs 64.38 +/- 20.23 and 72.35 +/- 18.43, p = .124). Also, the Ep values of the aorta between group T1 and T2 rabbits were significantly different (p = .033). Light and transmission electron microscopy confirmed morphologic typical changes of aortic atherosclerosis in groups T1 and T2. Grayscale sonography with the ET method could be used to evaluate tissue elastic changes in arterial walls associated with atherosclerosis and hypercholesterolemia.

Detection of lipid in atherosclerotic vessels using ultrasound-guided spectroscopic intravascular photoacoustic imaging

Lipid is a common constituent in atherosclerotic plaques. The location and area of the lipid region is closely related to the progression of the disease. Intravascular photoacoustic (IVPA) imaging, a minimally invasive imaging modality, can spatially resolve the optical absorption property of arterial tissue. Based on the distinct optical absorption spectrum of fat in the near infrared wavelength range, spectroscopic IVPA imaging may distinguish lipid from other water-based tissue types in the atherosclerotic artery. In this study, a bench-top spectroscopic IVPA imaging system was used to ex-vivo image both atherosclerotic and normal rabbit aortas. By combing the spectroscopic IVPA image with the intravascular ultrasound (IVUS) image, lipid regions in the aorta were identified. The results demonstrated that IVUS-guided spectroscopic IVPA imaging is a promising tool to differentiate lipid in atherosclerosis.

Atherosclerosis: Contrast-enhanced MR Imaging of Vessel Wall in Rabbit Model—Comparison of Gadofosveset and Gadopentetate Dimeglumine

To investigate the potential of gadofosveset for contrast material-enhanced magnetic resonance (MR) imaging of plaque in a rabbit model of atherosclerosis. All experiments were approved by the animal ethics committee. Thirty-one New Zealand White rabbits were included in one of four study groups: animals with atherosclerosis imaged with gadofosveset (n = 10) or gadopentetate dimeglumine (n = 7) and control animals imaged with gadofosveset (n = 7) or gadopentetate dimeglumine (n = 7). Aortic atherosclerosis was induced through endothelial denudation combined with a cholesterol-enriched diet. Control rabbits underwent a sham surgical procedure and received a regular diet. After 8 weeks, pre- and postcontrast T1-weighted MR images of the aortic vessel wall were acquired. Relative signal enhancement was determined with dedicated software. Statistical analysis was performed by using a generalized linear mixed model. Immunohistochemical staining with CD31 and albumin was used to assess microvessel density and the albumin content of the vascular wall. Group differences were analyzed by using a chi(2) test. Gadofosveset spatial distribution and content within the vessel wall were determined with proton-induced x-ray emission (PIXE) analysis. Postcontrast signal enhancement was significantly greater for atherosclerotic than for control animals imaged with gadofosveset (P = .022). Gadopentetate dimeglumine could not enable discrimination between normal and atherosclerotic vessel walls (P = .428). PIXE analysis showed higher amounts of gadopentetate dimeglumine than gadofosveset in both atherosclerotic and normal rabbit aortas. Immunohistochemical staining revealed the presence of albumin and increased microvessel density in the vascular walls of atherosclerotic rabbits. These results suggest that gadofosveset can be used to differentiate between atherosclerotic and normal rabbit vessel walls. http://radiology.rsnajnls.org/cgi/content/full/250/3/682/DC1.

Spectroscopic intravascular photoacoustic imaging to differentiate atherosclerotic plaques

The potential of intravascular photoacoustic (IVPA) imaging to detect atherosclerosis was previously demonstrated using a 532 nm nanosecond pulsed laser and an intravascular ultrasound (IVUS) imaging catheter. However, to differentiate vulnerable plaques, the composition of plaques needs to be imaged. Therefore, we introduce a multi-wavelength photoacoustic imaging method to distinguish various types of plaques. Multi-spectral IVPA imaging of ex vivo samples of normal and atherosclerotic rabbit aorta was performed at several wavelengths within 680-900 nm range. The spectral variation of photoacoustic response was extracted and a spectroscopic analysis was performed. The results of our preliminary study suggest that the spectroscopic intravascular photoacoustic imaging technique can be used to differentiate fibrous and lipid components of the atherosclerotic plaques.

Remote Temperature Estimation in Intravascular Photoacoustic Imaging

Intravascular photoacoustic (IVPA) imaging is based on the detection of laser-induced acoustic waves generated within the arterial tissue under pulsed laser irradiation. In general, laser radiant energy levels are kept low (20 mJ/cm 2) during photoacoustic imaging to conform to general standards for safe use of lasers on biological tissues. However, safety standards in intravascular photoacoustic imaging are not yet fully established. Consequently, monitoring spatio-temporal temperature changes associated with laser-tissue interaction is important to address thermal safety of IVPA imaging. In this study we utilize the IVUS-based strain measurements to estimate the laser-induced temperature increase. Temporal changes in temperature were estimated in a phantom modeling a vessel with an inclusion. A cross-correlation–based time delay estimator was used to assess temperature-induced strains produced by different laser radiant energies. The IVUS-based remote measurements revealed temperature increases of 0.7 ± 0.3°C, 2.9 ± 0.2°C and 5.0 ± 0.2°C, for the laser radiant energies of 30 mJ/cm 2, 60 mJ/cm 2 and 85 mJ/cm 2, respectively. The technique was then used in imaging of ex vivo samples of a normal rabbit aorta. For arterial tissues, a temperature elevation of 1.1°C was observed for a laser fluence of 60 mJ/cm 2 and lesser than 1°C for lower energy levels normally associated with IVPA imaging. Therefore, the developed ultrasound technique can be used to monitor temperature during IVPA imaging. Furthermore, the analysis based on the Arrhenius thermal damage model indicates no thermal injury in the arterial tissue, suggesting the safety of IVPA imaging. (E-mail: emelian@mail.utexas.edu)

Classification of atherosclerotic rabbit aorta samples by mid-infrared spectroscopy using multivariate data analysis

Atherosclerotic and normal rabbit aorta samples show a marked difference in chemical composition governed by the water, lipid, and protein content. The strongly overlapping infrared absorption features of the different constituents, and the complexity of the tissue matrix, render tissue classification by direct evaluation of molecular spectroscopic characteristics obtained from IR reflectance or attenuated total reflectance (ATR) measurements virtually impossible. We apply multivariate analysis and classification techniques based on partial least squares regression (PLS) and linear discriminant analysis to IR spectroscopic data obtained by IR-ATR measurements and reflectance IR microscopy with high predictive accuracy during blind testing. Training data are collected from atherosclerotic and normal rabbit aorta samples. These results demonstrate the potential of IR spectroscopy combined with multivariate classification strategies for the in-vitro identification of normal and atherosclerotic aorta tissue. The prospect for future in-vivo measurement concepts is also discussed.

Classification of Atherosclerotic Rabbit Aorta Samples with an Infrared Attenuated Total Reflection Catheter and Multivariate Data Analysis

The strongly overlapping infrared absorption features of atherosclerotic and normal rabbit aorta samples as governed by their water, lipid, and protein content render the direct evaluation of molecular characteristics obtained from infrared (IR) spectroscopic measurements challenging for classification. We have successfully applied multivariate data analysis and classification techniques based on partial least squares regression (PLS), linear discriminant analysis (LDA), and principal component regression (PCR) to IR spectroscopic data obtained by using a recently developed infrared attenuated total reflectance (IR-ATR) catheter prototype for future in vivo diagnostic applications. Training data were collected ex vivo from atherosclerotic and normal rabbit aorta samples. The successful classification results on atherosclerotic and normal aorta samples utilizing the developed data evaluation routines reveals the potential of spectroscopy combined with multivariate classification strategies for the identification of normal and atherosclerotic aorta tissue for in vitro and, in the future, in vivo applications.

ATP depletion in macrophages in the core of advanced rabbit atherosclerotic plaques in vivo

The cores of rabbit plaques in vivo are hypoxic, suggesting that ATP depletion due to an insufficient supply of oxygen and nutrients could contribute to macrophage death in atherosclerotic plaques. During hypoxia, however, macrophages maintain ATP levels by anaerobic glycolysis. To directly assess ATP and glucose metabolites in plaques in vivo, we used bioluminescence imaging to map the concentrations of ATP, glucose, glycogen, and lactate in normal and atherosclerotic rabbit aortas in vivo. Hypoxia was assessed with NITP (7-(4′-(2-nitroimidazol-1-yl)-butyl)-theophylline). Normal aortas and plaques <500 μm thick were not hypoxic and had homogenous concentrations of energy metabolites. In plaques >500 μm thick, however, the cores were characterized by ATP depletion, low concentrations of glucose and glycogen, and a high concentration of lactate. A majority of ATP-depleted macrophages within the core were viable but severely hypoxic and glucose depleted. Hyperoxia in vitro reversed the ATP depletion in macrophages in viable areas of the core. Our findings suggest that ATP depletion contributes to the death of macrophages in atherosclerotic lesions and to the formation of a necrotic core.

Differential expression of proteoglycans biglycan and decorin during neointima formation after stent implantation in normal and atherosclerotic rabbit aortas

Proteoglycans decorin and biglycan, which bind to TGF-β, are thought to participate in regulation of extracellular matrix accumulation in arterial intimal hyperplasia. To investigate the correlation of these proteoglycans with the cellular localization and phenotypic modulation of smooth muscle cells (SMCs), we analyzed the spatial and chronological distribution of these proteoglycans and two cytokines, TGF-β and IL-1β, in the process of neointima formation after stent implantation in the aortas of rabbits fed a high-cholesterol diet (atherosclerotic group) or a regular diet (control group). We implanted metallic stents in the rabbit aortas and harvested the aortas 4–56 days later for immunohistochemical and mRNA in situ hybridization analyses. In the control group, TGF-β and biglycan expression was in correspondence with the chronology and localization of embryonic SMCs. In the atherosclerotic group, TGF-β and biglycan expression was sustained throughout the experimental period, which was in accord with the prolonged expression of embryonic SMCs. Decorin, which did not occur in neointima in the control group, appeared in the atherosclerotic aortas in the confined area of vascular SMCs surrounding the macrophages around the stent wire. These results indicate that biglycan and decorin kinetics during neointima formation after arterial injury are distinct, despite their similar construction; biglycan synthesis correlates with embryonic SMCs.

Metabolic evidence for sequestration of low density lipoprotein in abdominal aorta of normal rabbits

In rabbits, atherosclerosis develops preferentially at branch sites compared with the adjacent uniform aorta. This study investigated the hypothesis that low-density lipoprotein (LDL) is “sequester...

Vascular actions of brain natriuretic peptide: modulation by atherosclerosis and neutral endopeptidase inhibition

ObjectivesWe sought to define the vascular actions of the cardiac hormone brain natriuretic peptide (BNP) on cellular proliferation and cyclic guanosine monophosphate (cGMP) in human aortic vascular smooth muscle cells (HAVSMCs). Secondly, we investigated BNP and acetylcholine (ACh) vasorelaxations in aortic rings from normal and atherosclerotic rabbits in the presence and absence of long-term oral inhibition of neutral endopeptidase (NEP).BackgroundThe vascular actions of BNP are not well defined, despite the presence of its receptor in vascular smooth muscle and the upregulation of NEP, the ectoenzyme that degrades BNP, in the vascular wall in atherosclerosis.MethodsHAVSMCs stimulated with fetal calf serum (FCS) were pulsed with bromodeoxyuridine (BrdU) with and without BNP. The HAVSMCs were incubated in the presence and absence of BNP to assess cGMP. Vasorelaxations to BNP and ACh were assessed in rings in normal and atherosclerotic rabbits in the presence and absence of long-term oral inhibition of NEP, together with assessment of atheroma formation.ResultsFCS-stimulated BrdU uptake in HAVSMCs was suppressed with BNP. BNP potentiated cGMP in HAVSMCs. BNP resulted in potent vasorelaxation in normal isolated aortic rings, which were impaired in atherosclerotic versus normal rabbits and preserved with NEP inhibition, which also decreased atheroma formation. Relaxations to ACh, which were also impaired in atherosclerosis, were preserved with inhibition of NEP.ConclusionsWe conclude that BNP potently inhibits vascular smooth muscle cell proliferation and potentiates the generation of cGMP. BNP potently relaxes the normal rabbit aorta, and this response is impaired in atherosclerosis but preserved with inhibition of NEP, together with a reduction in atheroma formation and preservation of relaxations to ACh.

Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation.

The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Inducible endothelial cell adhesion molecules may participate in this process. In aortas of normal chow-fed wild-type mice and rabbits, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), but not E-selectin, were expressed by endothelial cells in regions predisposed to atherosclerotic lesion formation. En face confocal microscopy of the mouse ascending aorta and proximal arch demonstrated that VCAM-1 expression was increased on the endothelial cell surface in lesion-prone areas. ICAM-1 expression extended into areas protected from lesion formation. Hypercholesterolemia induced atherosclerotic lesion formation in rabbits, LDL receptor and apolipoprotein E knockout mice, and Northern blot analysis demonstrated increased steady-state mRNA levels of VCAM-1 and ICAM-1, but not of E-selectin. Immunohistochemical staining revealed that VCAM-1 and ICAM-1 were expressed predominantly by endothelium in early lesions and by intimal cells in more advanced lesions. In early and advanced lesions, staining was most intense in endothelial cells at and adjacent to lesion borders. ICAM-1 staining extended into the uninvolved aorta. These expression patterns were highly reproducible in both species. The only difference was that VCAM-1 expression in endothelium over the central portions of lesions was found frequently in rabbits and rarely in mice. The expression of VCAM-1 by arterial endothelium in normal animals may represent a pathogenic mechanism or a phenotypic marker of predisposition to atherogenesis.

Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 from the aortas of cholesterol fed rabbits partially counterbalances increased metalloproteinase activity.

The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) plays an important role in extracellular matrix turnover and thereby modulates atherosclerotic plaque development. MMP-1, -2, -3, and -9 activity is increased by atherosclerosis, but the status of TIMPs is less clear. We therefore compared secretion of TIMPs-1 and -2 from cultured aortic explants derived from arch, middle, and distal portions of thoracic aortas of normal rabbits and rabbits fed a 1% cholesterol diet for 8 weeks, using reverse zymography of conditioned media. Cholesterol feeding significantly increased secretion of TIMP-1 from arch and middle portions (both 2.6-fold), accompanied by 2.0- and 2.7-fold increases in TIMP-2, respectively. Atherosclerotic aortas exhibited increased immunoreactive TIMP-1 and TIMP-2 in endothelial cells, smooth muscle cells, and macrophages. Staining of extracellular matrix was also prominent within the noncellular boundary region between fibrous cap and the lipid core, and within the lipid core. Increased TIMP-2 staining was also found in the media subjacent to the lipid core. In situ gelatin zymography demonstrated excess MMP activity within the plaque with partial inhibition in the lipid core base and subjacent media, consistent with the distribution of TIMPs. Casein zymography and in situ zymography demonstrated that increased caseinolytic activity was confined to the pericellular zones of macrophages within the lipid core, again consistent with its restriction by TIMPs. In summary, atherosclerosis increases TIMP expression, which counterbalances, in part, increased MMP activity.

A bioluminescence method for the mapping of local ATP concentrations within the arterial wall, with potential to assess the in vivo situation.

According to the anoxemia theory of atherosclerosis, an imbalance between the demand for and supply of oxygen and nutrients in the arterial wall is a key factor in atherogenesis. However, the energy metabolic state of the arterial tissue in vivo is largely unknown. We applied a bioluminescence method, metabolic imaging, to study local ATP concentrations in cryosections of normal pig and atherosclerotic and normal rabbit aorta. Some vessels were subjected to energy metabolic restrictions by incubation at different oxygen and glucose concentrations and others were rapidly frozen in liquid nitrogen to reflect the in vivo situation. Local ATP concentrations and the ATP distribution at a microscale was dependent on oxygen as well as glucose concentrations during incubation. ATP depletion was seen in the mid media of pig aorta in all incubations, but only at low oxygen concentration without glucose in the media of the thinner rabbit aorta. ATP-depleted zones were seen deep in pig media (>750 microm from the lumen) and in rabbit plaques (>300 micrometer+ from the lumen) even at high oxygen (pig 75% O2 and rabbit 21% O2) and glucose concentrations (5.6 mmol/L glucose). This observation probably illustrates an insufficient diffusion of glucose, which highlights the importance of studying the conditions for diffusion not only of oxygen but also of other metabolites in the arterial wall. In rapidly frozen vessels the medial ATP concentration was shown to be 0.6 to 0.8 micromol/g wet weight (both pig and rabbit aorta) and in pig aorta a gradient could be seen indicating higher ATP concentrations at the lumenal side. We propose that metabolic imaging, as applied to snap-frozen tissue, may be used to assess the energy metabolic situation in the arterial wall in vivo. The spatial resolution allows the detection of local variations within the arterial tree. However, steep concentration gradients (eg, near the border of the tissue) will be underestimated. The method may be extended to include determinations of glucose and lactate concentrations and will be used in parallel with an established method to assess hypoxia in the arterial wall in vivo.

Association between secondary flow in models of the aorto-celiac junction and subendothelial macrophages in the normal rabbit

In order to examine the association between arterial fluid dynamics and the distribution of subendothelial macrophages in the normal rabbit aorta, steady and pulsatile particle flow visualization was performed in a geometrically realistic model of the rabbit aorto-celiac junction region. Over a range of aorto-celiac steady flow ratios, particle pathlines along the upstream lateral aortic walls curved to enter the celiac orifice, while two asymmetric regions of reversing spiral secondary flow originated along the downstream lateral portions of the orifice flow divider. These regions increased in size as either the Reynolds number or flow into the celiac artery increased. In pulsatile flow studies, particles along the lateral aortic walls near the celiac orifice began to spiral into the branch during peak systole. During systolic deceleration, the size of this spiral flow region increased as particles reversed direction to enter the celiac orifice. This contrasted with flow patterns directly upstream and downstream of the orifice, which remained unidirectional throughout this period even along the distal lip of the orifice. The highest frequency of subendothelial white blood cells in the normal rabbit aorta was associated with regions where secondary flow patterns occurred, and where the orientation of endothelial cell nuclei deviated from the major direction of aortic flow. Secondary flow patterns may aid the accumulation of monocytes and macrophages about the lateral regions of the celiac artery flow divider by transporting monocytes to the walls, allowing them time to attach to the endothelial cells, or by stimulating the endothelial cells to express leukocyte adhesion molecules. These same regions are associated with increased endothelial permeability to low density lipoprotein and, under hypercholesterolemic conditions, lesion origination.

Expression of alpha2-adrenergic receptors in normal and atherosclerotic rabbit aorta.

Alpha2-adrenergic receptors (alpha2-ARs) in vascular smooth muscle cells are known to mediate vasoconstriction; however, it is unknown which of the 3 subtypes of alpha2-AR (alpha2A, alpha2B, or alpha2C) is expressed in vascular tissue. We have used subtype-specific probes in in situ hybridization and RNase protection assays to analyze the expression of alpha2-AR in the thoracic aorta of New Zealand White (NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits, a model for atherosclerosis. We found that the alpha2A-AR mRNA was in endothelial and smooth muscle cells in both NZW and WHHL aorta. In addition, the shoulders and subendothelial regions of the atherosclerotic lesions in WHHL aorta showed abundant expression of alpha2A-AR mRNA. Antibodies to macrophage (RAM-11) and smooth muscle cell (HHF-35) antigens were used to localize macrophage and smooth muscle cells in aortic sections from WHHL rabbits. The expression of alpha2A-AR mRNA within the lesions of WHHL rabbits correlated with the presence of infiltrating macrophages. We discuss the potential role of alpha2A-ARs in macrophage function and in promoting atherosclerosis.