Segment Of Abdominal Aorta Research Articles

Human Amniotic Fluid Stem Cells Reduce Neointimal Formation and Inflammation in a Model of Aortic Allograft Vasculopathy

Introduction: Chronic allograft vasculopathy (CAV) is a major limiting factor of long-term allograft survival. Although some mechanisms involved in CAV have already been identified, there is no specific treatment for this clinical condition. Considering the immune-inflammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. In this context, human amniotic fluid derived stem cells (hAFSC), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, may represent an alternative strategy. hAFSC display immunomodulatory properties, express mesenchymal and embryonic markers, show high proliferation rates, but do not induce tumor formation and their use does not raise ethical issues. Based on these observations, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. Methods: Experimental aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. The abdominal aorta segment, obtained from the emergency of renal arteries until its bifurcation, was orthotopically anastomosed in syngeneic or allogeneic recipients. hAFSC were isolated from amniotic fluid of 16-20 weeks pregnant women, who underwent amniocentesis due to advanced maternal age. Briefly, these cells were cultivated in Dulbecco's modified Eagle's medium-low glucose (DMEM-low) supplemented with 10% fetal bovine serum. hAFSC were purified using their characteristic to adhere to plastic culture dishes, characterized by flow cytometry, and characterized by their potential osteogenic, adipogenic, and chondrogenic differentiation. In addition, RT-PCR experiments demonstrated that these hAFSC express OCT-4 4/5 and NANOG. Rats were divided into 3 groups: syngeneic (SYNG), untreated F344 receiving syngeneic aorta from F344 (n=8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n=8); and ALLO+hAFSC, ALLO rats treated with hAFSC (106 cells) (n=8). Histological analysis and immunohistochemistry were performed 30 days post transplantation. Results: Neointima formation was not observed in the SYNG group. However, the intimal thickness was dramatically increased in the ALLO group accompanied by a high number of ED1+ and CD43+ cells, and enhanced expression of α-SMA in the neointima. Treatment with hAFSC attenuated neointimal thickness and induced a significant decrease of ED1+, CD43+ cells as well as α-SMA expression in the neointima. Table 1: Effects of hAFSC in experimental aortic allograft vasculopathy.Table: No Caption available.Conclusion: These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration in the intima, possibly through immunomodulatory properties, which may have contributed to ameliorate vascular lesions in CAV.

1026 EARLY BRIEF TREATMENT WITH ANGIOTENSIN CONVERTING ENZYME INHIBITOR, PERINDOPRIL, PREVENTS AORTIC CALCIFICATION IN ADULT SPONTANEOUSLY HYPERTENSIVE RATS

Background: Aortic calcification is a potent risk marker of cardiovascular events. Aortic calcification contributes to arterial stiffness and increased pulse pressure. Early angiotensin converting enzyme inhibition (ACEi) in spontaneously hypertensive rats (SHR) during a critical treatment window prevents aortic stiffness in adulthood. However, the effect of ACEi on aortic calcification is unknown. Method: ACEi (perindopril, 3 mg/kg/day, by gavage) was delivered during the pre- (6-10 weeks, SHR(Tx)y, n = 6) and established (20-24 weeks of age, SHR(Tx)o, n = ?) hypertensive phases. Vascular stiffness of the thoracic and abdominal aortic segments at their corresponding anaesthetised mean aortic pressure (MAP) was calculated from beat-to-beat pulse wave velocity (PWV) measurements in-vivo, using two 1.4F pressure catheters introduced to the thoracic and abdominal aorta, positioned a known distance apart. Aortas were harvested post-mortem and divided into thoracic and abdominal segments at the renal bifurcation for quantification of calcium content using atomic absorption spectrophotometry. Results were compared to untreated SHR, and the normotensive control strain, Wistar-Kyoto (WKY). Results: Perindopril significantly decreased MAP (-43%, P=0.0005), isobaric thoracic PWV (-19%, P=0.002) but not abdominal PWV. Thoracic aorta of the SHR(Tx)y group calcified 54% less than that of SHR controls (p=0.001), and approximated values of the normotensive control strain, with no difference detected in the abdominal aorta (p=0.09). The SHR(Tx)o group did not differ from SHR controls in any measured parameters. Conclusion: This study shows direct evidence of the persistent effect of early, but not late, ACEi in prevention of arterial stiffness associated with hypertension and corresponding aortic calcification.

Anatomic differences of the distal aorta with dilatation or aneurysm between patients from Asia and Europe as seen on CT imaging

AimThe hypothesis of this research is that there are differences in morphology of dilated and aneurysm changed infrarenal aorta between the patients from Europe and Asia that are important for endovascular treatment. Authors analyzed the morphologic differences of the infra-renal segment of abdominal aorta (a.a.) and the iliac arteries, common iliac artery (c.i.a.) between the Asians and Europeans examined by computed tomography (64 MD CT) from the point of the clinical use of the endovascular stent-graft. Materials and methodsThe research was conducted simultaneously in Europe and in Asia and 60 patients with distal aorta aneurysm were included (30 of each ethnic origin). The examinations were conducted at the identical types of 64 MD CT equipment, and under same conditions of examination technique and post-processing. ResultsThere were statistically significant differences in regard to important morphology criteria for a.a. and c.i.a. between patients with the aneurysm from Asia and the Europe.Analysis was preformed referring to the gender, age, body weight (BW), height, body mass index (BMI), body surface (SA index), and various diameters of a.a. and c.i.a. at several linear and transversal levels, angle and volume of the aneurysm. The biggest differences relate to the width of the central part of aneurysm of a.a. and the length and volume of c.i.a. ConclusionThere were statistically significant differences in regard to important morphology criteria for a.a. and c.i.a. between patients with the aneurysm from Asia and the Europe.

Prediction of Coronary Conduit Artery Endothelial Cell Phenotype by Phenotypic Assessment in the Systemic Vasculature

Human studies have established a correlation between endothelial vasomotor function assessed at the brachial and coronary arteries. This relationship spurred widespread investigation of brachial artery vasomotor function and, more recently, the isolation and phenotypic analysis of endothelial cells harvested invasively from the brachial artery (presumably with the application of understanding the coronary vascular endothelium). However, notwithstanding the correlation between vasomotor function in brachial and coronary arteries, the degree to which markers of endothelial cell phenotype correlate between systemic and coronary arteries is unknown. PURPOSE: Determine the degree to which endothelial cell phenotype assessed in peripheral conduit vessels is predictive of phenotype in the coronary artery endothelium in swine. METHODS: Isolated segments of thoracic and abdominal aorta, carotid, brachial, femoral, renal, internal mammary, and right coronary arteries were harvested at the time of sacrifice from 19 swine. Vessels were placed in a dissection buffer, cleaned of excess connective tissue, cut longitudinally, and the endothelium was mechanically scraped yielding an endothelial enriched sample of vascular cells. Samples were subsequently probed for eNOS, HSP90, p67phox, SOD1 and SOD3 protein expression via immunobloting. RESULTS: Expression of eNOS, HSP90, SOD1, and SOD3 was on average well correlated (p < 0.05 vs. coronary artery for each vessel) between systemic conduit arteries and the right coronary artery (mean rho value = 0.71 ± 0.02, 0.83 ± 0.02, 0.72 ± 0.02, and 0.91 ± 0.01 for eNOS, HSP90, SOD1, and SOD3, respectively). In contrast, expression of p67phox in systemic conduit artery endothelium was not correlated to that in the right coronary artery (mean rho value = 0.24 ± 0.04, p > 0.05 vs. coronary artery for each vessel). CONCLUSION: We conclude that endothelial cell protein expression assessed in peripheral conduit arteries is predictive of expression levels in the conduit coronary arteries in the cases of some (e.g., eNOS, HSP90, SOD1 and SOD3) but not all (e.g., p67phox) markers of endothelial cell phenotype. Supported by: P01-HL052490 (M.H.L.) and T32-AR048523 (G.H.S. and J.P.).

Expression of AT1‐R, AT2‐R and Mas‐R in placental and aortic tissue during normal pregnancy and pregnancy‐induced hypertension in rats

Pregnancy is associated with blunted response to angiotensin II (Ang II). In contrast, there is an increased pressor response to this peptide in pregnancy-induced hypertension (PIH). The mechanisms involved in these changes have not been elucidated. The aim of this work was to determine if pregnancy-induced hypertension changes the vascular protein expression of Ang II receptors (AT1, AT2), and Ang 1–7 Mas receptor (Mas-R) from placenta and thoracic and abdominal aorta segments in rats. We used a subrenal aorctic coarctation (SRAC) model in female Wistar rats as an experimental model of PIH. Tissue samples were homogenized and immunoblotted using Anti-AT1R, AT2-R and Anti-Mas antibody. We found a differential regional expression of both receptors AT1 and AT2 in normal pregnancy, with a higher AT1R expression along the aorta and placenta during pregnancy-induced hypertension. We also found that Mas-R is also differentially expressed in healthy aortic tissue, and falls during PIH in both segments, while in the placental tissue from hypertensive rats expression was higher in comparison with healthy pregnant rats. In conclusion, these data suggest that vascular AT1 receptor expression and Mas-R might have a pathophysiological role in PIH, contributing to Ang II vascular hypersensitivity and lack of dilating response. Supported by SIP-IPN 20100012 and 20101460 grants.

Parsing Aortic Aneurysms

See related article, pages 574–581 Aortic aneurysms are progressive enlargements of the aorta that can lead to life-threatening degenerative changes in the structure of the artery wall including medial dissections and wall rupture. The abdominal aorta is the most common site of aneurysm formation, yet the ascending thoracic aorta can also exhibit aneurysmal expansion with potentially dire outcomes. Ascending aortic aneurysms are frequently associated with connective tissue diseases such as Marfan's syndrome, a disorder of the extracellular matrix protein fibrillin-1.1 Mouse models carrying hypomorphic mutations in fibrillin-1 also develop aortic dilations associated with macrophage infiltration, elastin fragmentation, and enhanced transforming growth factor (TGF)β signaling in the artery wall.2 Aortic aneurysms in fibrillin-1 hypomorphic mice can be prevented by treatment with either anti-TGFβ neutralizing antibodies or with the angiotensin II (Ang II) type 1 (AT1) receptor antagonist losartan.3 Indeed, chronic infusion of Ang II into apoE −/− mice is an effective experimental model to induce aortic aneurysm formation and to study the molecular pathways underlying its pathogenesis.4 Ang II signals through 2 types of angiotensin receptors, AT1 and AT2.5 AT2 receptors have been shown to elicit antiproliferative responses in vascular smooth muscle cells (SMCs), possibly by antagonism of signaling through AT1 receptors.5 In mice, the AT1 receptor exists as 2 subtypes, AT1a and AT1b, and both receptor subtypes are expressed in the artery wall. The receptor that mediates angiotensin-induced contractile responses in vascular smooth muscle is predominantly the AT1b subtype.6 The AT1 receptor subtype that mediates aortic aneurysm formation has been unknown. In a study that appears in this issue of Circulation Research , Rateri et al used a series of mouse models to genetically dissect the process of Ang II–induced aneurysm …

Atorvastatin Reduces Calcification in Rat Arteries and Vascular Smooth Muscle Cells

To examine the in vivo effects of atorvastatin (AT) on arterial calcification in rats, arterial calcification was established by subcutaneous injection of vitamin D3 and Warfarin. Intragastric administration of AT began 4 days before establishment of arterial calcification in the AT group (n=6). Blood samples were taken and abdominal aortas were collected and stained. After induction of calcification, plasma Ca(2+) levels in the CA and AT groups were significantly higher than those before treatment and in the untreated controls. Plasma Ca(2+) levels in the AT group were significantly lower than in the CA group. The relative calcification area in aortic specimens from the AT group was significantly smaller than in the CA group. Rat aortic vascular smooth muscle cells (VMSC) were isolated from abdominal aortic segments and pre-treated with AT (1, 5, or 10 μM) for 24 hr. Cells in the calcification (CA) group and the AT group were cultured with β-glycerophosphate, insulin and vitamin C for 14 days to induce cell calcification. Calcium deposition and alkaline phosphatase activity were significantly increased in the CA group compared to untreated controls (p<0.01). This effect was ameliorated by AT (all p<0.01). In vivo administration of AT reduced arterial calcification and plasma Ca(2+) concentration. In vitro, AT reduced calcification markers in rat aortic vascular smooth muscle cells.

Renal allograft function not impacted by extensive aortic dissection.

A 63-year-old hypertensive male underwent renal transplantation from his nephew in 2005. In 2007, he was diagnosed with aortic dissection—Stanford type A and B with aortic aneurysm. He had resection of the aortic aneurysm and replacement of the ascending aorta with a hemi-arch graft with left coronary artery implantation. In January 2010, he presented with chest pain, fever and malaise. Blood pressure was 107/73 mmHg and pulse 96/min and the femoral, anterior tibial, posterior tibial and dorsalis pedis artery pulses were palpable bilaterally. Computed tomography (CT) chest scan showed left pleural effusion. Diagnostic pleural tap was bloody and positive for Mycobacterium tuberculosis by polymerase chain reaction. Blood urea was 21 mg/dL, creatinine 1.2 mg/dL, haemoglobin 10.7 g/dL, WBC 11 800 mm3, platelet count 173 000 mm3, total protein 6.3 g/dL, albumin 2.9 mg/dL, electrolytes normal and troponin-I 0.031 ng/mL. Maintenance immunosuppressives used were prednisone 5 mg OD, mycophenolate mofetil 500 mg BD and rapamycin 1 mg OD. Other medications used were isoniazid 300 mg OD, pyrazinamide 750 mg BD, rifampicin 450 mg OD, levofloxacin 500 mg OD and vitamin B6 20 mg OD. CT angiogram showed normal ascending aorta with previous aortic repair. Dissection originated distal to left subclavian artery with dense contrast-filled false lumen and poorly filled true lumen. The dissection had a spiral course extending up to proximal segments of the iliac arteries (Figure 1). The abdominal aortic segment was not dilated. The origin of the artery for the transplant kidney and visceral arteries was the true lumen. The false lumen extended up to the left common iliac artery (Figure 2). This patient, with an unusual presentation of aortic dissection, and probably with a leaking aneurysm due to an infective pathology caused by Mycobacterium tuberculosis, had good allograft function as the transplant renal artery originated from the true lumen of the right common iliac artery maintaining adequate perfusion. He continues to have a good graft function 4 months later. Fig. 1 Dissection extending up to iliac arteries. Fig. 2 Transplant kidney and the vascular supply. Conflict of interest statement. None declared.

Treatment of abdominal aorta aneurysms

Background The best treatment of abdominal aorta aneurysms of the segments below the emergency of the renal arteries are still under discussion. In literature there are several studies that compare the retroperitoneal (R.P.) approach with the transperitoneal (T.P.) one or that suggest their possible variations. The R.P. approach offers the possibility of treating patients with hostyle abdomen (former laparotomic surgery, obesity) or in a state of chronic respiratory insufficiency; it allows for a better exposure of the over and infra-renal abdominal aorta segments and most of all it is characterised by a better post surgery period associated with a lower number of post-operatory complications with a faster restart of the intestinal functions and with shorter hospitalization.

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure

An ideal animal model of abdominal aortic aneurysm (AAA) is of great importance for clarifying unknown complex mechanisms of the pathogenesis. We introduce a new, simple technique to create reliable AAAs that simulate human aneurysms. Experimental models of AAAs were created in 71 rats by means of a 20-minute application of intraluminal elastase (30 U) and extraluminal calcium chloride (0.5M) in the 1-cm segment of infrarenal abdominal aorta (group EC, n = 26). A single application of elastase (group E, n = 24) or calcium chloride (group C, n = 21) was used as control. The treated aorta in each group was measured under physiologic conditions and harvested at 1 and 4 weeks. Successful AAA formation was defined as a dilation ratio >50%. Inflammatory response, elastolytic activity, and histology in the treated aorta were evaluated among the three groups. The surgical procedure in each group was similarly completed for approximate 30 minutes and performed without any technical failure or operative death. At 4 weeks, the dilation ratio and wall thickness were 94.8% +/- 9.9% and 125.4 +/- 5.6 microm in group EC, 43.3% +/- 6.3% and 149.6 +/- 6.5 microm in group E, and 10.9% +/- 4.2% and 152.9 +/- 7.2 microm in group C. The success rate of AAA formation in group EC (92.7%) was significantly higher than that in group E (25.0%) and group C (0.0%). Less elastin content in the aortic wall was observed in group EC. At 1 week, tumor necrosis factor-alpha and interleukin-1beta messenger RNA (mRNA) expressions were significantly upregulated, and CD3+ and CD11b+ cells were significantly infiltrated into the treated aorta of group EC, compared with groups E or C. Gelatinolytic activities and mRNA expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were also significantly activated in group EC. The rat AAA model using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure is simple and easy to perform and is highly reliable and reproducible to create a saccular aneurysm similar to human AAAs. This model could be more useful to clarify AAA pathogenesis, mechanisms, and treatment interventions in experimental researches.

Apoptosis-regulated survival of primarily extravascular cells in proliferative active poststent neointima

Increased proliferation, mitigated apoptosis, and recruitment of primarily extravascular cells to injured vessels are important processes during neointima formation. Therefore, the goal of this study was to assess the spatiotemporal balance between proliferation and apoptosis and the influence of apoptosis on the survival of primarily extravascular cells in in-stent neointima. Minipigs underwent stent implantation to abdominal aortic segments. At Days 1, 7, 14, 30, 60, and 90 after injury, arterial cross sections were analyzed by TUNEL assay to detect apoptotic cells. For immunohistochemical detection of Ki67+/proliferating cell nuclear antigen (PCNA)+ proliferative, caspase3+ apoptotic, S100+/fascin+ dendritic, GFAP+ neural crest-derived cells and CD14+ monocytes/macrophages, the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method was used. In the incipient cell-rich neointima, both frequency of proliferation and apoptosis was maximal (Ki67, 28.5±2.2%; PCNA, 25.4±3.8%; TUNEL, 8.6±0.4%; caspase3, 7.9±4.3%). With time, parallel to the decline in the neointima cellularity, signaling for proliferation and apoptosis decreased. Throughout the time course of neointima development, the apoptotic activity was detected in primarily extravascular cells. Imbalance between proliferation and apoptosis and recruitment of dendritic cells, monocytes/macrophages, and neural crest-derived cells to the injured vessels may partly explain the formation of the hypercellular in-stent neointima. Herein, apoptosis is an important factor that regulates survival of primarily extravascular neointimal cells.

Arquitetura da parede vascular de segmentos torácico e abdominais da aorta de macaco prego (Cebus apella)

O segmento torácico da aorta em macaco prego apresentou na túnica íntima uma lâmina elástica interna evidente, estando também presente em todos os segmentos aórticos abdominais analisados nesta espécie. A túnica média aórtica, ao nível torácico, mostrou uma quantidade média de 23,12 lâminas elásticas, tendo disposição circular e oblíqua em relação à luz vascular, e a túnica adventícia apareceu formada por fibras colágenas, dispostas irregularmente entre uma quantidade relativamente menor de fibras elásticas e de fibras musculares lisas. A túnica média do segmento abdominal aórtico, neste primata, observada ao nível supra-renal, apresentou em média 19,12 lâminas elásticas que apareceram relativamente desorganizadas e fragmentadas. Ao nível aórtico infra-renal, foram evidenciadas, na túnica média 11,75 lâminas elásticas, em média, e próximo da emissão das artérias ilíacas comuns a túnica média aórtica tinha cerca de 8,37 lâminas elásticas, as quais estavam entremeadas por fibras musculares lisas e por fibras colágenas que aparentavam aumentar a sua concentração próximo à adventícia. A lâmina elástica externa só foi visível no segmento abdominal aórtico mais distal, ou seja, próximo da emissão das artérias ilíacas comuns.

Endothelial Cell Apoptosis is Responsible for the Formation of Coronary Thrombotic Atherosclerotic Plaques

Ischemic manifestations of atherosclerosis are mainly due to thrombus formation upon superficially eroded (denudation of luminal endothelium) plaques or deeply ruptured (fibrous cap rupture) plaques. Eroded plaques, atherosclerotic plaques without rupture, are found common in young patients of sudden death with coronary thrombosis. Our study aimed to investigate the role of endothelial cell (EC) apoptosis in eroded plaque with thrombosis using an atherosclerotic rabbit model. Atherosclerotic plaques were established by post-balloon-injury high-cholesterol feeding in 33 rabbits. After three-month feeding, a 2-cm segment of plaque-rich abdominal aorta for each animal was clamped in vivo and filled with staurosporine, which induces endothelial apoptosis, or saline for 20 minutes. Three days later, serum lipids and high sensitive C-reactive protein (hs-CRP), a valuable inflammatory parameter, were quantified, and abdominal aorta angiography was conducted. In addition, immunohistochemistry staining was performed for all processed aortae. In the staurosporine-treated aorta, endothelium integrity of plaques was disrupted partially or in large areas, but fibrous cap rupture was not observed, the findings of which were similar to eroded plaques detected in human subjects. As compared to saline controls, staurosporine-treated rabbits showed higher apoptosis scores and thrombotic scores, and more angiographic overt thrombosis and histological thrombosis (P < 0.01, respectively), despite the similar serum levels of lipids and hs-CRP. We further confirmed that apoptosis score was linearly associated with thrombotic score. These results suggest that endothelial apoptosis may be an independent risk factor for thrombosis. In conclusion, the increase in endothelial apoptosis is involved in the formation of thrombotic eroded plaques.

Atherosclerotic Peripheral Vascular Disease Symposium II

The Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group was commissioned by the American Heart Association (AHA) to provide a forum to address important and emerging issues in this multidisciplinary area of clinical science. The working group was a primary outgrowth of the AHA Atherosclerotic Vascular Disease Conference held in Boston, Mass, in July 2002. It was created in recognition of the fact that atherosclerosis is a systemic disease with important sequelae in many regional circulations in addition to the heart, including the brain, kidneys, mesentery, and limbs. Its mission is to provide a forum for the multiple disciplines engaged in research, evaluation, and management of patients with noncoronary atherosclerosis. The goals of the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group are to develop a strategy to increase awareness of atherosclerotic vascular disease, identify important gap areas in knowledge that require further clinical investigation, and develop programs that will facilitate prevention and treatment of peripheral atherosclerotic diseases. Developments in research and technology that are relevant to atherosclerotic vascular disease are emerging rapidly. As a result, greater opportunities to translate science to clinical practice are available. The American College of Cardiology/AHA practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic) provide many evidenced-based recommendations for diagnosing and treating patients with atherosclerotic vascular diseases.1 Nevertheless, in some areas, the evidence has not matured sufficiently for definitive guidelines. Some of these areas have engendered considerable controversy among practitioners. Among these are the efficacy and outcome of screening programs for vascular disease and the appropriate and timely use of endovascular interventions. Accordingly, the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group convened the second AHA conference on Atherosclerotic Vascular Disease, which took place in Boston, Mass, in July 2006. The conference was also sponsored by the …

Optimization of the Model of Abdominal Aortic Aneurysm – Experiment in an Animal Model

Background: Many studies have been performed in order to model abdominal aortic aneurysm (AAA) in an experimental animal, most commonly in small laboratory animals. In our study, we tried to find the best AAA model in a pig by using various mechanical and enzymatic mechanisms. Methods: Twenty-two pigs were operated on. We combined 3 mechanisms of creating an AAA, using an intraluminal infusion of porcine pancreatic elastase into the abdominal aortic segment, application of plastic cuff below the renal arteries causing turbulent blood flow, and inserting a patch into the longitudinal aortotomy. Results: We found different results in different groups according to the mechanisms used. In group A, with a combination of the intraluminal elastase infusion and application of a stenosing cuff, AAA developed in all 7 animals (100%). In this group, we also found the largest histological changes in the abdominal aorta samples. Conclusion: The use of intraluminal pancreatic elastase infusion, together with increased turbulent flow caused by the stenosing cuff, seems to be the best model of AAA in pigs. This model is suitable for further research in the etiopathology of AAA. In fact, it is the first successful approach to a large-caliber native aneurysm model.

Investigation into the onset and progression of transplant arteriosclerosis in a mice aortic retransplantation model

Long-term function of vascularized human organ grafts is often limited by transplant arteriosclerosis and can lead to graft failure. Here, we have analyzed the impact of an initial rejection episode on the later development of transplant arteriosclerosis. Following transplantation of allogeneic abdominal aortic segments in mice, aortic grafts were retransplanted into either immunodeficient or syngeneic recipients. Retransplantation of grafts from immunocompetent into immunodeficient mice as early as 2 days after the primary transplant resulted in intimal proliferation and obstruction of the graft lumen 30 days after the primary transplant. In contrast, retransplantation of the grafts into donor syngeneic B10 recipients within 7 days did not result in the development of transplant arteriosclerosis. These data suggest that the adaptive immune system can induce intimal proliferation by an initial lethal hit that is sustained by the innate response. However our data demonstrate that development of chronic rejection can be inhibited, in this case by retransplantation into a syngeneic host.

Cells of Primarily Extravascular Origin in Neointima Formation following Stent Implantation

Objectives: In-stent restenosis due to neointima formation is a major limitation following stent implantation. Recently, several studies reported mobilization of primarily extravascular cells to the arterial sites after balloon angioplasty. Therefore, the goal of the present study was to assess the coordinated neointimal expression of endothelial progenitor, dendritic and neural crest-derived cells after stent implantation. Methods: Male minipigs underwent stent implantation in abdominal aortic segments. Animals were sacrificed at 1, 7, 14, 30, 60 or 90 days. Cross sections of the injured vessels were obtained for immunohistochemistry using specific antibodies for the detection of endothelial progenitor (CD133), dendritic (S100) and neural crest-derived cells (GFAP), as well as monocytes/macrophages (CD14) and T lymphocytes (CD3). Results: As a key finding, frequency of CD133, S100, GFAP, CD14 and CD3 (18.5 ± 3.6, 14.9 ± 1.8, 10.6 ± 1.1, 40.2 ± 8.3 and 5.0 ± 0.6%, respectively) in neointima was maximal at day 7. With ongoing neointima enlargement, expression of these cells decreased. In advanced neointima, labeled cells were predominantly localized at luminal and stented sites. Media showed almost no immunoreactivity of the markers studied, whereas adventitial zones of neovascularization revealed some signals. Conclusions: Endothelial progenitor, dendritic, neural crest-derived and inflammatory cells are consistently recruited into arterial neointima, mostly at early time points after stent implantation.

Effect of osmolarity on the zero-stress state and mechanical properties of aorta

Some pathological conditions may affect osmolarity, which can impact cell, tissue, and organ volume. The hypothesis of this study is that changes in osmolarity affect the zero-stress state and mechanical properties of the aorta. To test this hypothesis, a segment of mouse abdominal aorta was cannulated in vivo and mechanically distended by perfusion of physiological salt (NaCl) solutions with graded osmolarities from 145 to 562 mosM. The mechanical (circumferential stress, strain, and elastic modulus) and morphological (wall thickness and wall area) parameters in the loaded state were determined. To determine the osmolarity-induced changes of zero-stress state, the opening angle was observed by immersion of the sectors of mouse, rat, and pig thoracic aorta in NaCl solution with different osmolarities. Wall volume and tissue water content of the rings were also recorded at different osmolarities. Our results show that acute aortic swelling due to low osmolarity leads to an increase in wall thickness and area, a change in the stress-strain relationship, and an increase in the elastic modulus (stiffness) in mouse aorta. The opening angle, wall volume, and water content decreased significantly with increase in osmolarity. These findings suggest that acute aortic swelling and shrinking result in immediate mechanical changes in the aorta. Osmotic pressure-induced changes in the zero-stress state may serve to regulate mechanical homeostasis.

Glucose Modulates Basement Membrane Fibroblast Growth Factor-2 via Alterations in Endothelial Cell Permeability

The effects of glucose extremes on vascular physiology and endothelial cell function have been examined across a range of time scales. Not unexpectedly, chronic glucose exposure induces long term tissue effects. Yet short term exposure can also impose lasting consequences. The persistence of vascular pathology after euglycemic restoration further suggests a glucose exposure memory. Slow turnover reservoirs such as basement membrane are candidates for prolongation of acute events. We hypothesized that glucose-induced vascular dysfunction is related to altered vasoactive compound handling within the endothelial cell-basement membrane co-regulatory unit. Endothelial cell basement membrane-associated fibroblast growth factor-2 increased linearly with culture glucose within days of elevated glucose exposure. Surprisingly, basement membrane fibroblast growth factor-2 binding kinetics remained unchanged. The glucose-induced increase in basement membrane fibroblast growth factor-2 was instead related to enhanced endothelial cell fibroblast growth factor-2 release and permeability. Cellular fibroblast growth factor-2 release occurred concomitant with apoptosis but was not blocked by caspase inhibitors. These data suggest that release was associated with sub-lethal early apoptotic cell membrane damage, perhaps related to reactive oxygen species formation. High glucose basement membrane in turn enhanced endothelial cell proliferation in a fibroblast growth factor-2-dependent manner. We now show that glucose-induced alterations in endothelial cell function promote changes in basement membrane composition, and these changes further affect endothelial cell function. These data highlight the interrelationship of cell and basement membrane in pathological conditions such as hyperglycemia. These phenomena may explain long term effects on the endothelium of short term exposure to glucose extremes.

Screening, analysis and in vitro vasodilatation of effective components from Ligusticum Chuanxiong

Effective components, ligustilide and butylidenephthalide, from Ligusticum Chuanxiong ( Ligusticum wallichii Franchat, Umbelliferae) were screened and identified by using a cell membrane chromatography (CMC) and a gas chromatography/mass spectrometry (GC/MS). The components showed the effects of inhibiting vasoconstriction in vitro on rat abdominal aorta segments. The screening procedure was performed in a rat artery CMC column (50 mm × 2.0 mm I.D.) with a sodium phosphate buffer (pH 7.4) as mobile phase at 37 °C. The identification was accomplished by a DB-5MS 30 m capillary column (0.25 mm I.D., 0.25 μm film thickness) with helium as carrier gas operating under program control temperature and electron impact ionization mass spectrometer in a scan mode. Results demonstrated that ligustilide and butylidenephthalide can act on rat artery cell membrane similar to verapamil in CMC system. They significantly inhibited the vasoconstrictions induced by norepinephrine bitartrate (NE) and calcium chloride (CaCl 2). The relaxing effect of ligustilide on the NE- and CaCl 2-induced constrictions is more potent than that of butylidenephthalide. Ligustilide and butylidenephthalide seem to be the two main effective components of Ligusticum Chuanxiong as a traditional Chinese medicine for treating blood vessel diseases.