Development and Evaluation of Virola oleifera Formulation for Cutaneous Wound Healing.

In regions adjacent to the Brazilian Atlantic Forest, Virola oleifera (VO) resin extract has been popularly used for decades as a skin and mucosal healing agent. However, this antioxidant-rich resin has not yet been investigated in wound healing, whose physiological process might also be aggravated by oxidative stress-related diseases (e.g., hypertension/diabetes). Our aim, therefore, was to investigate whether VO resin presents healing effects through an innovative cream for topical applications. For this, adult male Wistar rats were divided into four groups. Then, four 15 mm excisions were performed on the shaved skin. All treatments were applied topically to the wound area daily. At the end of experiments (0, 3rd, and 10th days) macroscopic analysis of wound tissue contraction and histological analysis of inflammatory cell parameters were performed. The group treated with VO cream showed the best wound contraction (15%, p < 0.05) and reduced levels of lipid peroxidation and protein oxidation (118% and 110%, p < 0.05, respectively) compared to the control group. Our results demonstrated the healing capacity of a new formulation prepared with VO, which could be, at least in part, justified by antioxidant mechanisms that contribute to re-epithelialization, becoming a promising dermo-cosmetic for the treatment of wound healing.

Bisphenol A contamination in infant rats: molecular, structural, and physiological cardiovascular changes and the protective role of kefir.

The effects of bisphenol A (BPA) contamination on the cardiovascular function still are not clear. Here, we evaluated the vascular effects of BPA and the protective actions of kefir in infant rats. Animals (25 days old) were treated with BPA (100 µg/Kg/day) for 60 days (BPA group), or administered kefir (0.3 mL/100 g) in addition to BPA (BPA kefir group), compared with non-treated rats (Control group).The vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine and specific blockers. The balance between reactive oxygen species (ROS) and nitric oxide (NO) was assessed through flow cytometry in the vascular tissue. The BPA group developed high blood pressure (+10%) and the analysis of vascular reactivity showed an impaired ACh-induced relaxation (~80%). The further analysis by using NADPH, NOS and COX blockers revealed that the impaired vasorelaxation was due to increased ROS production (+12%), NO bioavailability (-12%) and increased vasoconstriction to prostanoids (+36%) compared with the Control group. Kefir treatment reverted those effects significantly. Analysis of the aortic cells showed increased •O2- production (1942±39 a.u.) and decreased NO bioavailability (1250±30 a.u.) compared with the Control group (1374±146 and 2777±25 a.u., P<.05) and kefir reverted these values (1298±57 and 2517±57 a.u.). Contamination by BPA in this model caused hypertension and endothelial dysfunction and it was accompanied by a vascular ROS/NO imbalance, damage of endothelial layer and pro-apoptotic effects. The novelty is that the treatment using probiotic kefir was able to attenuate the progression the above BPA effects.

In vitro evaluation of barium titanate nanoparticle/alginate 3D scaffold for osteogenic human stem cell differentiation.

Nanomaterials can mimic properties of extracellular matrix molecules, promising great potential for scaffold composition in tissue engineering. In the present study, we investigated whether barium titanate nanoparticles (BT NP) combined with alginate polymer would provide a new cytocompatible three-dimensional (3D) scaffold to induce osteogenic stem cell differentiation. In vitro cytocompatibility and osteogenic differentiation potential were investigated using human mesenchymal stem cells (MSC). Firstly, we studied the cell viability and oxidative stress by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) thiazolyl blue tetrazolium bromide (MTT) and superoxide dismutase (SOD) assays. Overall, neither pure BT NP or BT NP/alginate 3D scaffold induced cytotoxicity. The scanning electron and atomic force microscopy revealed that BT NP/alginate 3D scaffold produced exhibited highly interconnected pores and surface nanotopography that were favorable for MSC differentiation. Von Kossa staining showed mineralization nodules and MSCs morphology changed from spindle to cuboid shape after 21 d. Finally, BMP-2 and ALP mRNA were significantly upregulated on cells grown into the BT NP/alginate 3D scaffold. Thus, the BT NP/alginate 3D scaffold showed an osteogenic differentiation induction potential, without the addition of osteogenic supplements. These results indicate that the BT NP/alginate 3D scaffold provides a cytocompatible and bioactive microenvironment for osteogenic human MSC differentiation.

Low Doses of G-CSF Prevent Cerebral Infarction and Maintain Muscle Strength in an Experimental Model of Global Ischemic Stroke.

BACKGROUND: Stroke is a major cause of severe and long-term disability in adult individuals. Treatment of this disease is limited by the narrow therapeutic window in which intervention is crucial. An alternative therapy for stroke could be cellular growth factors, which participate in several pathways that mediate neuronal cell death. METHODS: We evaluated the neuroprotective ability of different doses of granulocyte colonystimulating factor (G-CSF; 5, 50 and 100 µg/kg/day) in the mouse model of global cerebral ischemia induced by bilateral occlusion of the common carotid arteries for 80 minutes. The control group received vehicle (5% glucose solution) and the treated group was administered with G-CSF at two postsurgery time-points: immediately after and 24 hours after. Subsequently, muscle strength, leukocyte count, infarcted cortical area, and apoptosis/TUNEL were evaluated. RESULTS: The global ischemia promoted an impairment of the strength (16%) and a cerebral infarction (0.437±0.08 cm2) which were accompanied by apoptosis evaluated by TUNEL in control mice. In mice treated with G-CSF the strength function was maintained, the infarcted area (~70%) and apoptosis were decreased in a similar magnitude in all treated groups. Accordingly, the cytokine activities were confirmed by blood leukocyte count that was increased approximately 2-fold than that observed in the control group. CONCLUSION: The results indicate a neuroprotective effect of G-CSF, even in small doses, in mice subjected to global cerebral ischemia, thereby reducing the neurofunctional impairment caused by stroke, when considering the maintenance of muscle strength in the treated animals.

Beneficial Morphofunctional Changes Promoted by Sildenafil in Resistance Vessels in the Angiotensin II-Induced Hypertension Model.

BACKGROUND: By acting on multiple targets and promoting diverse actions, angiotensin II (Ang II) plays a pivotal role in vascular function. Recent studies suggested that phosphodiesterase-5 (PDE-5) inhibitors exhibit therapeutic effects in cardiovascular diseases. Here, the effects of sildenafil on vascular disturbances were analyzed in a mouse model of Ang II-induced hypertension. METHODS AND RESULTS: Male C57BL/6 mice were used as untreated animals (control) or infused with Ang II (1000 ηg/kg/min) for 28 days and treated with sildenafil (40 mg/kg/min) or vehicle (Ang II) during the last two weeks. After 4 weeks, the Ang II animals exhibited a high systolic blood pressure (186±3 mmHg vs. 127±3 mmHg for control mice), which was attenuated by sildenafil (163±7 mmHg). The mesenteric vessels from the Ang II animals revealed damage to the endothelial layer, an increase in the cross-section area (1.9-fold) and vascular cell production of peroxynitrite (512±13 a.u.), which was ameliorated in the Ang II-Sil group (1.2-fold and 400±17 a.u.). Analysis of the vascular responsiveness showed an increased contractility response to norepinephrine in Ang II animals (Rmax: 70%), which was abolished by sildenafil through increased nitric oxide (NO) bioavailability and decreased reactive oxygen species (ROS) and vasoconstrictor prostanoids. CONCLUSION: Sildenafil attenuates the morphofunctional deleterious effects of Ang II on resistance vessels. The benefits of sildenafil seem to occur through restoring the balance of ROS/NO/eicosanoids. Therefore, this study opened new avenues for further clinical targeting of the treatment of cardiovascular diseases related to activation of the renin-angiotensin system.

Probing the Sulfur-Modified Capping Layer of Gold Nanoparticles Using Surface Enhanced Raman Spectroscopy (SERS) Effects.

Gold nanoparticles (AuNP) exhibit particular plasmonic properties when stimulated by visible light, which makes them a promising tool to many applications in sensor technology and biomedical applications, especially when associated to sulfur-based compounds. Sulfur species form a great variety of self-assembled structures that cap AuNP and this interaction rules the optical and plasmonic properties of the system. Here, we report the behavior of citrate-stabilized gold nanospheres in two distinct sulfur colloidal solutions, namely, thiocyanate and sulfide ionic solutions. Citrate-capped gold nanospheres were characterized using ultraviolet-visible (UV-Vis) absorption, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and atomic force microscopy (AFM). In the presence of sulfur species, we have observed the formation of NP clusters and chain-like structures, giving rise to surface-enhanced effects. Surface-enhanced Raman spectroscopy (SERS) pointed to a modification in citrate vibrational modes, which suggests substitution of citrate by either thiocyanate or sulfide ions with distinct dynamics, as showed by in situ fluorescence. Moreover, we report the emergence of surface-enhanced infrared absorption (SEIRA) effect, which corroborates SERS conclusions. Further, SEIRA shows a great potential as a tool for specification of sulfur compounds in colloidal solutions, which is particularly useful when dealing with sensor technology.

Fructose intake exacerbates the contractile response elicited by norepinephrine in mesenteric vascular bed of rats via increased endothelial prostanoids.

Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected.

Ultrasound-assisted extraction of Achyrocline satureioides prevents contrast-induced nephropathy in mice.

Achyrocline satureioides or Macela, has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and to treat various digestive disorders. The aim of the present study was to evaluate the preventive action of the extracts of A. satureioides obtained by maceration and ultrasound-assisted extraction, quercetin and N-acetylcysteine against contrast-induced nephropathy in mice. The antioxidant activity, cytotoxicity and inhibition of nitric oxide (NO) production in macrophages were evaluated. Also, chemical analyses of phenolic compounds, total flavonoids, and quercetin by LC-MS/MS present in various extracts of A. satureioides were performed. Thirty six mice were divided into six groups: control group (C), Contrast-Induced Nephropathy group (CIN), Group N-acetylcysteine 200mg/kg (NAC); Group quercetin 10mg/kg (Q), Group Macela 10mg/kg (M10), and Group Macela 50mg/kg (M50). The serum levels of urea and creatinine, advanced oxidation protein products (AOPP) and renal ultrastructure were evaluated by electron microscopy scanning. Ultrasound-assisted extraction improved the quality of extract (with 100% ethanol), since did not show toxicity to fibroblasts, and showed potent antioxidant activity and a high content of phenolic compounds, flavonoids, and quercetin, in addition to being able to reduce the production of NO in dose-dependent effect in macrophages. Results showed that animals treated with Macela extracts maintained normal levels of urea, creatinine, and AOPP, while preserving ultrastructure of the renal cells. The obtained results were more promising than NAC and Q groups in protecting against renal failure caused by CIN, showing that the plant can be a promising drug for preventing this disease.

Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

BACKGROUND: The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). METHODS: SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. RESULTS: Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment. CONCLUSIONS: Kefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.

Sildenafil Improves Vascular Endothelial Structure and Function in Renovascular Hypertension.

In translational medicine, the discovery of new drugs or new potential uses for currently available drugs is crucial for treating the resistant hypertension associated with renal artery stenosis. The phosphodiesterase 5 inhibitor sildenafil has been shown to reduce blood pressure and to improve the endothelium-dependent relaxation in the two kidney, one clip (2K1C) mouse model of renovascular hypertension. In the present study, we evaluated the effects of sildenafil (40 mg/kg/day for two weeks) on the endothelial structure and contractile function in mesenteric resistance arteries 28 days after clipping the renal artery. The data showed an enhanced vascular contractile response to norepinephrine in 2K1C hypertensive mice (56%) when compared with Sham mice, which was associated with increased oxidative stress and with a thinning of endothelial cells. Sildenafil treatment caused a significant amelioration in the enhanced contractile responsiveness (18%), which was associated to the recovery of the endothelial surface and abolishment of the oxidative stress. These data suggest that sildenafil could be considered a promising therapeutic option to manage endothelial dysfunction and hypertension in resistant patients.

Renovascular hypertension leads to DNA damage and apoptosis in bone marrow cells.

Angiotensin II (Ang II), which plays a pivotal role in the pathophysiology of the two-kidney, one-clip (2K1C) Goldblatt hypertension, has been associated with augmented generation of reactive oxygen species (ROS) in some cells and tissues. In the present study, we evaluated the influence of 2K1C hypertension on oxidative stress, DNA fragmentation, and apoptosis of bone marrow (BM) cells. Two weeks after the renal artery clipping or Sham operation, flow cytometry analysis showed a higher production of superoxide anions (approximately sixfold) and hydrogen peroxide (approximately twofold) in 2K1C hypertensive than in Sham normotensive mice. 2K1C mice also showed an augmented DNA fragmentation (54%) and apoptotic cells (21%). Our data show that the 2K1C renovascular hypertension is characterized by an increased production of ROS, DNA damage, and apoptosis of BM, which is a fundamental source of the cells involved in tissue repair.

DNA damage and augmented oxidative stress in bone marrow mononuclear cells from Angiotensin-dependent hypertensive mice.

It has been proposed that the nonhemodynamic effects of angiotensin II are important for the damage observed in the two-kidney, one-clip (2K1C) renovascular hypertension model. Much evidence confirms that angiotensin II is directly involved in NAD(P)H oxidase activation and consequent superoxide anion production, which can damage DNA. The current study was performed to examine the effects of angiotensin-II-dependent hypertension in bone marrow mononuclear cells (BM-MNC); dihydroethidium staining was used to assess reactive oxygen species (ROS) production, and the comet assay was used to assess DNA fragmentation in 2K1C hypertensive mice 14 days after renal artery clipping. In this study we demonstrated that 2K1C hypertensive mice have an elevated lymphocyte count, while undifferentiated BM-MNC counts were diminished. 2K1C mice also showed an augmented ROS production and marked BM-MNC DNA fragmentation. In conclusion, endogenous renin angiotensin system activation-induced arterial hypertension is characterized by excessive ROS production in BM-MNC, which might cause marked DNA damage.

Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice.

BACKGROUND: Stem/progenitor cell-based therapy has successfully been used as a novel therapeutic strategy for vascular diseases triggered by endothelial dysfunction. The aim of this study was to investigate the effects of mononuclear cell (MNC) therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE-/-) mouse. METHODS: Spleen-derived MNCs were isolated from green fluorescent protein (GFP)-transgenic mice for cell treatment. A cuff-induced thrombus model was produced by placing a nonconstrictive silastic collar around the left common carotid artery in 20-week-old female apoE-/- mice. After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff-MNC) or vehicle (Cuff-Vehicle) and were compared with sham-operated animals (Sham). RESULTS: The histological analysis showed that the MNC treatment reverted occlusive thrombus formation compared to the vehicle and the vessel lumen area to that observed in the Sham group (MNC, 50 ± 4; Vehicle, 20 ± 4; Sham, 55 ± 2 x10³ µm²; p < 0.01). The animals that underwent the carotid cuff placement developed compensatory vessel enlargement, which was reduced by the MNC therapy. In addition, the treatment was able to reduce superoxide anion production, which likely contributed to the reduced apoptosis that was observed. Lastly, the immunofluorescence analysis revealed the presence of endothelial progenitor cells (EPCs) in the carotid endothelia of the apoE-/- mice. CONCLUSION: In situ short-term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid arteries of apoE-/- mice, possibly through the homing of EPCs, reduction of oxidative stress and decreased apoptosis.

Granulocyte colony stimulating factor prevents kidney infarction and attenuates renovascular hypertension.

BACKGROUND: G-CSF is a critical regulator of hematopoietic cell proliferation, differentiation and survival. It has been reported that G-CSF attenuates renal injury during acute ischemia-reperfusion. In this study we evaluated the effects of G-CSF on the renal and cardiovascular systems of 2K1C hypertensive mice. METHODS: Male C57BL/6 mice were subjected to left renal artery clipping (2K1C) or sham operation and were then administered G-CSF (100 µg/kg/day) or vehicle for 14 days. RESULTS: Arterial pressure was higher in 2K1C + vehicle animals than in 2K1C + G-CSF (150±5 vs. 129±2 mmHg, p<0.01, n=8). Plasma angiotensin I, II and 1-7 concentrations were significantly increased in 2K1C + Vehicle when compared to the normotensive Sham group. G-CSF prevented the increase of these vasoactive peptides. The clipped kidney/contralateral kidney weight ratio showed a less atrophy of the ischemic kidney in the treated group (0.50±0.02 vs. 0.66±0.01, p<0.05). The infarction area in the clipped kidney was completely prevented in 7 out of 8 2K1C + G-CSF mice. Administration of G-CSF protected the clipped kidney from apoptosis. CONCLUSION: Our data indicate that G-CSF prevents kidney infarction and markedly attenuates the increases in plasma angiotensin levels and hypertension in 2K1C mice, reinforcing the protective effect of G-CSF on kidney ischemia.

Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice.

BACKGROUND: Recent studies have highlighted the potential of cell therapy for atherosclerosis. The aim of this study was to evaluate the effects of mononuclear cell (MNC) therapy on the development of atherosclerotic lesions in the apolipoprotein E knockout (apoE KO) mouse. METHODS: We investigated vascular lipid deposition, vascular remodeling, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in apoE KO mice treated with spleen MNCs isolated from lacZ transgenic mice (apoE KO-MNC) for 8 weeks compared to untreated control mice (apoE KO). RESULTS: Histological analysis of aortas showed a significant reduction in the lipid deposition area in apoE KO-MNC mice compared to apoE KO mice (0.051 ± 0.004 vs 0.117 ± 0.016 mm², respectively, p < 0.01). In addition, vessel morphometry revealed that MNC therapy prevented the outward (positive) remodeling in apoE KO mice that is normally observed (apoE KO-MNC: 0.98 ± 0.07 vs apoE KO: 1.37 ± 0.09), using wild-type mice (C57BL/6J) as a reference. ApoE KO-MNC mice also have reduced production of superoxide anions and increased eNOS expression compared to apoE KO mice. Finally, immunohistochemistry analysis revealed a homing of endothelial progenitor cells (EPCs) in the aortas of apoE KO-MNC mice. CONCLUSION: MNC therapy attenuates the progression of atherosclerosis in the aortas of apoE KO mice. Our data provide evidence that the mechanism by which this attenuation occurs includes the homing of EPCs, a decrease in oxidative stress and an upregulation of eNOS expression.

Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender.

BACKGROUND: Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO) mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice. METHODS: The grade (0 to 4) of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57) mice. RESULTS: Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive) remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68) using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice. CONCLUSION: The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.

Evaluation of aortic remodeling in apolipoprotein E-deficient mice and renovascular hypertensive mice.

BACKGROUND: The apolipoprotein E-deficient mouse (ApoE) spontaneously develops hypercholesterolemia and atherosclerotic lesions in large arteries. It is also known that angiotensin II-induced hypertension accelerates the development of atherosclerosis in ApoE mice. The objective of this study was to evaluate the aortic remodeling process in ApoE mice during the early phase of atherosclerosis in two-kidney one-clip hypertensive (2K1C) mice and in mice with the coexistence of atherosclerosis and arterial hypertension. METHODS: Renovascular hypertension was induced in 8- to 9-week-old C57BL/6 (C57) and ApoE and compared to sham animals 28 days later. C57-2K1C and ApoE-2K1C mice showed hypertension, tachycardia, and cardiac hypertrophy of similar magnitude. RESULTS: ApoE and ApoE-2K1C mice showed high levels of plasma cholesterol (4.8- and 3.6-fold) and aorta lipid deposition (85- and 101-fold) compared to C57 mice. The aorta lumen area was increased in C57-2K1C and ApoE-2K1C mice (0.57 +/- 0.04 and 0.55 +/- 0.02 mm(2)) compared to C57 mice (0.50 +/- 0.02 mm(2), p <0.05). The aorta wall area was increased by 20% in C57-2K1C and by 12% in ApoE-2K1C mice compared to C57 and ApoE. CONCLUSIONS: The main finding of this study was the absence of aorta remodeling in ApoE mice at the early stage of atherosclerosis and an outward remodeling of similar magnitude in C57-2K1C and ApoE-2K1C mice.