Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial.

Importance: Abdominal aortic aneurysms affect more than 3% of US older adults. Objective: To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter. Design, Setting, and Participants: Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018. Interventions: Patients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n = 133) or placebo (n = 128). Main Outcomes and Measures: The primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis ("normal scores"). Results: Of 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs -0.0258 (1-sided P = .71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, -0.07 to 0.07 cm; 2-sided P = .93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo. Conclusions and Relevance: Among patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms. Trial Registration: ClinicalTrials.gov Identifier: NCT01756833.

Normal Diameter and Growth Rate of Infrarenal Aorta and Common Iliac Artery in Chinese Population Measured by Contrast-Enhanced Computed Tomography.

BACKGROUND: In previous studies, the growth rate and diameter of infrarenal aorta was paucity of Chinese data. This study aim to evaluate the normal inside diameter and growth rate of the infrarenal aorta and common iliac artery in Chinese adult population and to explore the relationship between related factors and the arterial diameter. METHODS: A retrospective study was performed among 1,340 hospitalized adult patients undergoing contrast-enhanced abdominopelvic computed tomography from April 2017 to March 2018 in our hospital. The inside diameter of infrarenal aorta and common iliac artery was measured. Linear regression was used to analyze the relationship between various factors and arterial diameter. Kruskal-Wallis H test was used to analyze the relationship between the arterial diameter and age. Mann-Whitney U test was used to analyze the relationship between arterial diameter and sex. RESULTS: The inside diameter of the infrarenal aorta was 16.49 ± 2.12 mm in male patients and 14.50 ± 1.73 mm in female patients. In male patients, the right common iliac artery was 9.77 ± 1.75 mm, and the left was 9.65 ± 1.76 mm. In female patients, the right common iliac artery was 8.59 ± 1.31 mm and the left was 8.45 ± 1.28 mm. Comparing the oldest group with the youngest, the infrarenal aortic diameter increased 27.32% in male patients and 30.11% in female patients. Right common iliac artery increased 25.13% in male patients and 30.30% in female patients. Left common iliac artery increased 25.19% in male patients and 34.26% in female patients. The growth rate increased at the beginning, reached its peak at the age of 50-60 years, and then decreased. Multiple linear regression analysis results showed that sex, age, body surface area (BSA), hypertension, and cancer were significantly correlated with the diameter of infrarenal aorta. Sex, age, BSA, and hypertension were correlated with the diameter of right common iliac artery. Sex, age, BSA, and cancer were correlated with the diameter of left common iliac artery. CONCLUSIONS: The diameter of the infrarenal abdominal aorta and common iliac artery of Chinese people is smaller than that of other countries. The abdominal aortic aneurysm (AAA) guideline might be developed based on the basic diameter to suit patients with AAA and a different basic abdominal aortic diameter. Artery diameter was increased by the age, and female patients have smaller diameter and larger arterial growth rate than male patients. Female and young patients with AAA may choose more oversize grafts for endovascular AAA repair.

Sexo e idade e sua influência sobre a anatomia da aorta abdominal e seus ramos / Age and sex and their influence on the anatomy of the abdominal aorta and its branches

Resumo Contexto Não se sabe ao certo como a idade e o sexo do paciente influenciam na anatomia da aorta abdominal e de seus ramos. Objetivos Determinar os padrões anatômicos (diâmetro e angulações) mais frequentes da aorta abdominal e de seus ramos e a influência do sexo e da idade dos pacientes sobre esses padrões. Métodos Foram avaliadas tomografias computadorizadas de abdome com contraste endovenoso de 157 pacientes. Foram aferidos calibre e angulação de artérias abdominais em indivíduos de ambos os sexos, agrupados em cinco faixas etárias: 20 a 30 anos, 31 a 40 anos, 41 a 50 anos, 51 a 60 anos e 61 a 70 anos. Foram analisadas 18 variáveis: seis ângulos de emergências arteriais, nove diâmetros arteriais, taxas de dilatação, sexo e faixa etária. Para a obtenção das medidas, utilizou-se o programa de computador RadiAnt 4.2.1 DICOM viewer (Medixant, Poznan, Polônia). Resultados Entre as 157 tomografias, 69 eram de homens e 88, de mulheres. Apresentaram diferença estatística (p < 0,05): ângulo de origem e diâmetro da artéria mesentérica superior; ângulo e diâmetro das artérias renais; diâmetro das artérias ilíacas comuns; diâmetro e taxa de dilatação em diversos segmentos da aorta, exceto na porção proximal ao tronco celíaco. Conclusões Os diâmetros da aorta (em diversos segmentos) e de seus ramos (exceto da artéria renal esquerda) aumentam progressivamente com o passar da idade em ambos os sexos e são maiores e possuem taxa de dilatação mais elevada em homens do que em mulheres da mesma faixa etária. Entre os sexos, o ângulo de emergência da artéria mesentérica superior foi maior em homens, exceto entre 20 e 30 anos; o ângulo de origem da artéria renal esquerda foi maior em mulheres entre 51 e 60 anos.

Abstract Background It is not clear how patients' age and sex influence the anatomy of the aorta and its branches. Objectives To determine the most frequent anatomical patterns of diameter and angulation of the abdominal aorta and its branches and the influence of patients' sex and age on these patterns. Methods CT scans with intravenous contrast from 157 patients were analyzed. Diameter and angulations of the abdominal aorta and its branches were measured in individuals of both sexes, classified into five age groups: 20 to 30 years, 31 to 40 years, 41 to 50 years, 51 to 60 years, and 61 to 70 years. Eighteen variables were analyzed: 6 arterial origin angles, 9 arterial diameters, rate of diameter enlargement, and patient's sex and age. RadiAnt 4.2.1 DICOM viewer software was used for measurements. Results The total of 157 CT scans were from 69 men and 88 women. There were statistical differences (p <0.05) in the following results: angle of origin and diameter of the superior mesenteric artery; renal artery angle and diameter; diameter of the common iliac arteries, and diameter and rate of diameter enlargement of the aorta in several segments, but not the segment immediately proximal to the celiac trunk. Conclusions The diameters of several aorta segments and of its branches (except the left renal artery) increase progressively with age in both sexes and are larger and have a higher rate of diameter enlargement in men than in women in the same age ranges. Between sexes, the angle of origin of the superior mesenteric artery was larger in men, except between 20 and 30 years, and the angle of origin of the left renal artery was larger in women between 51 and 60 years old.

Differential growth patterns of the abdominal aorta and vertebrae during childhood.

The adult vertebral level of the splanchnic branches of the abdominal aorta relies on a complex series of fusion and regression steps during embryological development, such that variation is common. Little is known however regarding the anatomy of the abdominal aorta in children. This study aimed to investigate the spatial relationship between the abdominal aorta and the vertebral column during childhood development to inform clinical management of pediatric patients. Retrospective multislice computed tomography abdominopelvic angiograms of children aged neonate to 19 years (n = 232) were used to examine vertebral levels of the celiac trunk (CoT), superior mesenteric artery (SMA), inferior mesenteric artery (IMA), and aortic bifurcation (AB) using multiplanar formatting views in OsiriX. The abdominal aorta length, AB angle, and displacement of the aorta from the midline were quantified with the effect of age and sex analyzed using multinomial logistic regression and general linear models. The most frequent origins of CoT, SMA, IMA, and AB were T12, L1, L3, and L4, respectively, with significant variation in vertebral level for each vessel. SMA level was significantly more proximal with age, and CoT and AB demonstrated marked sex differences in vertebral level. As the age of the child increased, AB angle decreased, aortic displacement increased, and the length of the abdominal aorta increased at a slower velocity to the vertebral column (P < 0.001). Our study highlights the variation of the location and geometry of the abdominal aorta in children; this knowledge will positively impact pediatric surgical approaches and endovascular procedures. Clin. Anat. 32:783-793, 2019. © 2019 Wiley Periodicals, Inc.

Spatial Patterning of Molecular Cues and Vascular Cells in Fully Integrated Hydrogel Channels via Interfacial Bioorthogonal Cross-Linking.

Fully integrated hydrogel channels were fabricated via interfacial bioorthogonal cross-linking, a diffusion-controlled method for the creation and patterning of synthetic matrices based on the rapid bioorthogonal reaction between s-tetrazines (Tz) and trans-cyclooctene (TCO) dienophiles. Injecting an aqueous solution of a bisTCO cross-linker into a reservoir of tetrazine-modified hyaluronic acid (HA-Tz), while simultaneously drawing the syringe needle through the reservoir, yielded a cross-linked hydrogel channel that was mechanically robust. Fluorescent tags and biochemical signals were spatially patterned into the channel wall through time-dependent perfusion of TCO-conjugated molecules into the lumen of the channel. Different cell populations were spatially encapsulated in the channel wall via temporal alteration of cells in the HA-Tz reservoir. The interfacial approach enabled the spatial patterning of vascular cells, including human abdominal aorta endothelial cells, aortic vascular smooth muscle cells, and aortic adventitial fibroblasts, into the hydrogel channels with high viability and proper morphology in the anatomical order found in human arteries. The bioorthogonal platform does not rely on external triggers and represents the first step toward the engineering of functional and implantable arteries.

Aortic Elastic Properties in Preschool Children Born Preterm.

OBJECTIVE: Preterm birth predisposes children to the development of cardiovascular diseases in adulthood. The aim of this study was to characterize elastic properties of the aorta at preschool age and test the hypothesis that prematurity is associated with decreased aortic distensibility and increased stiffness, both of which are predictors of increased cardiovascular risk. APPROACH AND RESULTS: In an observational study of 76 five- to seven-year-old children born at a gestational age <32 weeks and 79 term-born controls, elastic parameters of the ascending and descending abdominal aorta were determined noninvasively by means of M mode echocardiographic tracings and calculated using computerized wall contour analysis. Compared with children born at term, the preterm group showed significantly reduced distensibility and increased stiffness of the descending abdominal aorta. These results remained significant under multivariable adjustment for birth weight z score, maternal smoking in pregnancy, maternal education, family history of cardiovascular disease, breastfeeding, childhood nutrition, and current body mass index z score (multivariable odds ratios and 95% confidence intervals 5.1, 1.7-15.9; P=0.005 and 2.8, 1.0-7.9; P=0.046, respectively). Further adjustment for intravenous lipid therapy attenuated the strength of association. Elastic properties of the ascending aorta did not differ between the 2 study groups. CONCLUSIONS: Children born preterm are characterized by decreased elastic properties of the descending abdominal aorta potentially attributable to impaired viscoelastic properties of and lipid damage to the aorta. Clinical follow-up of preterm infants with a focus on aortic elastic properties may be useful for tailoring early prevention programs and counteracting cardiovascular risk in adulthood.

Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides.

The clinical utility of a small-caliber vascular graft is still limited, owing to the occlusion of graft by thrombosis and restenosis. A small-caliber vascular graft (diameter, 2.5 mm) fabricated by electrospinning with a polyurethane (PU) elastomer (Pellethane) and biofunctionalized with heparin and two cell-adhesive peptides, GRGDS and YIGSR, was developed for the purpose of preventing the thrombosis and restenosis through antithrombogenic activities and endothelialization. The vascular grafts showed slightly reduced adhesion of platelets and significantly decreased adsorption of fibrinogen. In vitro studies demonstrated that peptide treatment on a vascular graft enhanced the attachment of human umbilical vein endothelial cells (HUVECs), and the presence of heparin and peptides on the graft significantly increased the proliferation of HUVECs. In vivo implantation of heparin/peptides coimmobilized graft (PU-PEG-Hep/G+Y) and PU (control) grafts was performed using an abdominal aorta rabbit model for 60 days followed by angiographic monitoring and explanting for histological analyses. The patency was significantly higher for the modified PU grafts (71.4%) compared to the PU grafts (46.2%) at 9 weeks after implantation. The nontreated PU grafts showed higher levels of α-SMA expression compared to the modified grafts, and for both samples, the proximal and distal regions expressed higher levels compared to the middle region of the grafts. Moreover, immobilization of heparin and peptides and adequate porous structure were found to play important roles in endothelialization and cellular infiltration. Our results strongly encourage that the development of small-caliber vascular grafts is feasible.

Segmental and age differences in the elastin network, collagen, and smooth muscle phenotype in the tunica media of the porcine aorta.

The porcine aorta is often used in studies on morphology, pathology, transplantation surgery, vascular and endovascular surgery, and biomechanics of the large arteries. Using quantitative histology and stereology, we estimated the area fraction of elastin, collagen, alpha-smooth muscle actin, vimentin, and desmin within the tunica media in 123 tissue samples collected from five segments (thoracic ascending aorta; aortic arch; thoracic descending aorta; suprarenal abdominal aorta; and infrarenal abdominal aorta) of porcine aortae from growing domestic pigs (n=25), ranging in age from 0 to 230 days. The descending thoracic aorta had the greatest elastin fraction, which decreased proximally toward the aortic arch as well as distally toward the abdominal aorta. Abdominal aortic segments had the highest fraction of actin, desmin, and vimentin positivity and all of these vascular smooth muscle markers were lower in the thoracic aortic segments. No quantitative differences were found when comparing the suprarenal abdominal segments with the infrarenal abdominal segments. The area fraction of actin within the media was comparable in all age groups and it was proportional to the postnatal growth. Thicker aortic segments had more elastin and collagen with fewer contractile cells. The collagen fraction decreased from ascending aorta and aortic arch toward the descending aorta. By revealing the variability of the quantitative composition of the porcine aorta, the results are suitable for planning experiments with the porcine aorta as a model, i.e. power test analyses and estimating the number of samples necessary to achieving a desirable level of precision. The complete primary morphometric data, in the form of continuous variables, are made publicly available for biomechanical modeling of site-dependent distensibility and compliance of the porcine aorta.

Prior Distributions of Material Parameters for Bayesian Calibration of Growth and Remodeling Computational Model of Abdominal Aortic Wall.

For the accurate prediction of the vascular disease progression, there is a crucial need for developing a systematic tool aimed toward patient-specific modeling. Considering the interpatient variations, a prior distribution of model parameters has a strong influence on computational results for arterial mechanics. One crucial step toward patient-specific computational modeling is to identify parameters of prior distributions that reflect existing knowledge. In this paper, we present a new systematic method to estimate the prior distribution for the parameters of a constrained mixture model using previous biaxial tests of healthy abdominal aortas (AAs). We investigate the correlation between the estimated parameters for each constituent and the patient's age and gender; however, the results indicate that the parameters are correlated with age only. The parameters are classified into two groups: Group-I in which the parameters ce, ck1, ck2, cm2,Ghc, and ϕe are correlated with age, and Group-II in which the parameters cm1, Ghm, G1e, G2e, and α are not correlated with age. For the parameters in Group-I, we used regression associated with age via linear or inverse relations, in which their prior distributions provide conditional distributions with confidence intervals. For Group-II, the parameter estimated values were subjected to multiple transformations and chosen if the transformed data had a better fit to the normal distribution than the original. This information improves the prior distribution of a subject-specific model by specifying parameters that are correlated with age and their transformed distributions. Therefore, this study is a necessary first step in our group's approach toward a Bayesian calibration of an aortic model. The results from this study will be used as the prior information necessary for the initialization of Bayesian calibration of a computational model for future applications.

Circumferentially aligned fibers guided functional neoartery regeneration in vivo.

An ideal vascular graft should have the ability to guide the regeneration of neovessels with structure and function similar to those of the native blood vessels. Regeneration of vascular smooth muscle cells (VSMCs) with circumferential orientation within the grafts is crucial for functional vascular reconstruction in vivo. To date, designing and fabricating a vascular graft with well-defined geometric cues to facilitate simultaneously VSMCs infiltration and their circumferential alignment remains a great challenge and scarcely reported in vivo. Thus, we have designed a bi-layered vascular graft, of which the internal layer is composed of circumferentially aligned microfibers prepared by wet-spinning and an external layer composed of random nanofibers prepared by electrospinning. While the internal circumferentially aligned microfibers provide topographic guidance for in vivo regeneration of circumferentially aligned VSMCs, the external random nanofibers can offer enhanced mechanical property and prevent bleeding during and after graft implantation. VSMCs infiltration and alignment within the scaffold was then evaluated in vitro and in vivo. Our results demonstrated that the circumferentially oriented VSMCs and longitudinally aligned ECs were successfully regenerated in vivo after the bi-layered vascular grafts were implanted in rat abdominal aorta. No formation of thrombosis or intimal hyperplasia was observed up to 3 month post implantation. Further, the regenerated neoartery exhibited contraction and relaxation property in response to vasoactive agents. This new strategy may bring cell-free small diameter vascular grafts closer to clinical application.

[Topography, relations and transformation of lumbar lymphatic sacs].

The peculiarities of the structure, skeletotopy, and syntopy of the lumbar lymphatic collector were studied on 20 5-8 week-old embryos and on 80 9-36 week-old fetuses using a complex macro-microscopic method. It is found that the lumbar lymphatic collector in fetuses at 9-10 weeks was represented by retroperitoneal and retroaortic lymphatic sacs that had a fusion mode of formation and were interconnected. Retroperitoneal sac was located in the projection of L(I)-L(IV) and was in contact with the anterior surface of the abdominal aorta and inferior vena cava, aortic lumbar paraganglia, abdominal aortic plexus and ganglia of sympathetic trunk. Retroaortic sack at L(I)-L(II) was adjacent to posterior surface of the aorta, the lumbar vertebrae and the medial crus of the diaphragm. These topical relations were preserved throughout the whole fetal period. However, in fetuses of 11-13 weeks lymphatic sacs formed the lymphatic plexuses, while in fetuses of 14-36 weeks they formed lumbar lymph nodes and their interconnecting vessels.

The normal growth of cross-sectional areas of the aorto-iliac segment in human fetuses - an anatomical, digital, and statistical study.

BACKGROUND: The intraluminal size of the aorto-iliac segment is relevant in both the clinical and echographic settings. The aim of this study was to compile both the absolute and relative age-specific reference intervals for cross-sectional areas (CSAs) of the aorto-iliac segment. MATERIAL/METHODS: Using the methods of anatomical dissection, digital-image analysis (Leica QWin Pro 16) and statistical analysis (Student's t test, one-way ANOVA, post-hoc RIR Tukey test, linear regression), the growth in CSA (in mm2) of the abdominal aorta, the common, external, and internal iliac arteries in 124 (60 males, 64 females) spontaneously aborted human fetuses aged 15-34 weeks was examined. RESULTS: No significant sex differences were found. In the age range of 4-9 months, the distal CSA of the abdominal aorta ranged from 0.87±0.34 to 19.18±3.36 mm2. The CSA of the common iliac artery varied from 0.37±0.22 to 4.30±1.54 mm2 on the right, and from 0.36±0.16 to 3.80±1.44 mm2 on the left. The sum of the CSAs of the right and left common iliac arteries grew proportionately to the distal CSA of the abdominal aorta; the latter being significantly larger than the former. On both sides, however, the CSA of the internal iliac artery was approximately twice that of the external iliac artery. Between the ages of 4 and 9 months, the CSA of the external iliac artery ranged from 0.10±0.06 to 1.32±0.52 mm2 on the right, and from 0.08±0.03 to 1.19±0.42 mm2 on the left. The CSA of the internal iliac artery increased from 0.23±0.14 to 2.59±1.22 mm2 on the right, and from 0.21±0.14 to 2.27±1.11 mm2 on the left. Bilaterally, the sum of the CSAs of the internal and external iliac arteries was significantly smaller than the CSA of the common iliac artery. The relative CSA of each artery decreased until the age of 6 months, after which their values were gradually increasing until the age of 9 months. CONCLUSIONS: The aorto-iliac segment does not reveal sex differences in its cross-sectional area. The cross-sectional area of the internal iliac artery is approximately twice the size of the external iliac artery. The aorto-iliac segment observed proximally to distally reduces its cross-sectional area, thereby resulting in an increase in blood velocity.

Normative growth data for the external diameters of the external and internal iliac arteries in human fetuses--an anatomical, digital and statistical study.

BACKGROUND: Normative data on the diameters of the aorto-iliac segment are extremely useful in the diagnosis and monitoring of prenatal arterial variants and pathologies. OBJECTIVES: The present study describes age-specific reference intervals and normal growth curves for the external diameters of the external and internal iliac arteries. MATERIAL AND METHODS: Using anatomical dissection and digital-image analysis, the normal growth of the external diameters of the external and internal iliac arteries was studied in 124 spontaneously aborted human fetuses, aged 15-34 weeks. RESULTS: Neither sex differences nor laterality differences were found. The external diameters of the external iliac arteries increased from 0.31 +/- 0.06 to 1.41 +/- 0.31 mm on the right, and from 0.29 +/- 0.04 to 1.37 +/- 0.24 mm on the left, and generated the following growth curves of best fit: y = 0.665 - 0.056 x Age + 0.002 x Age2 +/- 0.143 (R2 = 0.82) and y = 0.612 - 0.052 x Age + 0.002 x Age2 +/- 0.118 (R2 = 0.86), respectively. The external diameters of the internal iliac arteries were found to be statistically larger than those of the external iliac arteries (p = 0.0000). The external diameters of the internal iliac arteries ranged from 0.44 +/- 0.07 to 2.04 +/- 0.43 mm on the right, and from 0.44 +/- 0.06 to 1.83 +/- 0.43 mm on the left, and modeled the following quadratic functions: y = 1.524 - 0.127 x Age + 0.004 x Age2 +/- 0.242 (R2 = 0.74), and y = 1.391 - 0.117 x Age + 0.004 x Age2 +/- 0.220 (R2 = 0.76), respectively. The right external iliac arteries (in 71% of the cases) and the right internal iliac arteries (in 65.3% of cases) were larger in external diameter. CONCLUSIONS: The values of the external diameters of the external and internal iliac arteries are independent of sex. A strong trend towards higher values for the right external and internal iliac arteries is noted. The external diameter of the internal iliac artery is nearly 1.5 times greater than that of the external iliac artery. Surprisingly, normal growth of the external diameters of the external and internal iliac arteries follows quadratic functions.

Development of a growing rat model for the in vivo assessment of engineered aortic conduits.

BACKGROUND: Numerous limitations of aortic valve grafts currently used in pediatric patients cause the need for alternative prostheses. For the purpose of in vivo evaluation of novel engineered aortic conduit grafts, we aimed at downsizing a previously described model to create a growing rodent model. MATERIALS AND METHODS: U-shaped aortic conduits were sutured to the infrarenal aorta of young Wistar rats (70-80 g, n = 10) in an end-to-side manner. Functional assessment was performed by Doppler sonography and high resolution rodent MRI. Histology and immunohistochemistry followed after 8 wk. RESULTS: Postoperative recovery rate was 80%. Conforming to clinical observations, postoperative MRI (d 5) and Doppler sonography (wk 8) revealed unimpaired conduit perfusion. Explanted implants were luminally completely covered by an endothelial cell layer with local hyperplasia and accumulation of α-smooth muscle actin (+) cells. Moreover microcalcification of the decellularized scaffolds was observed. CONCLUSIONS: Our downsized model of aortic conduit transplantation enables overall characterization with detailed analysis of maturation of engineered aortic grafts in a growing organism.

Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.

BACKGROUND: The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression. RESULTS: We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007). CONCLUSIONS: Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.

Growth rate of affected aorta in patients with type B partially closed aortic dissection.

BACKGROUND: Our purpose was to evaluate the growth rate (GR) of the affected aorta and to clarify whether a partially closed false lumen can affect aortic enlargement in patients with type B double-barrelled aortic dissection (AD). METHODS: Seventy-one patients (mean age, 64.4 years) who had experienced AD were enrolled in this study. Regular follow-up computed tomography studies (mean, 48.9 months) were performed. During the follow-up period, aortic diameter was measured with computed tomography. The fastest GR was calculated. RESULTS: Based on final computed tomography findings, the patients were divided into three groups: those with completely closed false lumens (n = 8), those with partially closed false lumens (n = 20), and those with patent false lumens (n = 43). Among the patients with partially closed false lumens, 3 of 20 (15%) had a sac formation type and 17 (85%) had a non-sac formation type. The mean fastest GRs for groups with a completely closed false lumen, partially closed false lumen, and patent false lumen were -0.2 +/- 0.6, 4.0 +/- 4.3, and 4.9 +/- 4.5 mm/year, respectively. The differences among the three groups were statistically significant (p = 0.0149). In the partially closed false lumen group, the mean fastest GRs of the sac and non-sac formation types were 12.7 +/- 1.1 and 2.6 +/- 2.7 mm/year, respectively; this difference is statistically significant (p = 0.007). CONCLUSIONS: Affected aortas with partially closed false lumens do not exhibit the highest GR. The status of a partially closed false lumen is not a significant risk factor for enlargement; however, careful follow-up study is needed whenever the sac formation type of partially closed false lumen is identified.

Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice.

Atherosclerosis involves a macrophage-rich inflammation in the aortic intima. It is increasingly recognized that this intimal inflammation is paralleled over time by a distinct inflammatory reaction in adjacent adventitia. Though cross talk between the coordinated inflammatory foci in the intima and the adventitia seems implicit, the mechanism(s) underlying their communication is unclear. Here, using detailed imaging analysis, microarray analyses, laser-capture microdissection, adoptive lymphocyte transfers, and functional blocking studies, we undertook to identify this mechanism. We show that in aged apoE(-/-) mice, medial smooth muscle cells (SMCs) beneath intimal plaques in abdominal aortae become activated through lymphotoxin beta receptor (LTbetaR) to express the lymphorganogenic chemokines CXCL13 and CCL21. These signals in turn trigger the development of elaborate bona fide adventitial aortic tertiary lymphoid organs (ATLOs) containing functional conduit meshworks, germinal centers within B cell follicles, clusters of plasma cells, high endothelial venules (HEVs) in T cell areas, and a high proportion of T regulatory cells. Treatment of apoE(-/-) mice with LTbetaR-Ig to interrupt LTbetaR signaling in SMCs strongly reduced HEV abundance, CXCL13, and CCL21 expression, and disrupted the structure and maintenance of ATLOs. Thus, the LTbetaR pathway has a major role in shaping the immunological characteristics and overall integrity of the arterial wall.