Opening angle and residual strain in a three-layered model of pig oesophagus

Studies of various biological tissues have shown that residual strains are important for tissue function. Since a force balance exists in whole wall thickness specimens cut radially, it is evident that layer separation is an important procedure in the understanding of the meaning of residual stresses and strains. The present study investigated the zero-stress state and residual strain distribution in a three-layer model of the pig oesophagus. The middle part of the oesophagus was obtained from six slaughterhouse pigs. Four 3-mm-wide rings were serially cut from each oesophagus. Two of them were used for separating the wall into mucosa-submucosa, inner and outer muscle layers. The remaining two rings were kept as intact rings. The inner and outer circumferences and wall thickness of different layers in intact and separated rings were measured from the digital images in the no-load state and zero-stress state. The opening angle was measured and the residual strain at the inner and outer surface of different layers and the intact wall were computed. Compared with intact sectors (62.8+/-9.8 degrees ), the opening angles were smaller in the inner muscle sectors (37.2+/-11.4 degrees , P<0.01), whereas the opening angles of mucosa-submucosa (63.9+/-6.8 degrees ) and outer muscle sectors (63.9+/-6.8 degrees ) did not differ (P>0.1). Referenced to the zero-stress state of the intact sectors, the inner and outer residual strains of the intact rings was -0.128+/-0.043 and outer residual strain was 0.308+/-0.032. Referenced to the "true" zero-stress state of separated three-layered sectors, the inner residual strain of intact rings were -0.223+/-0.021 (P<0.01) and 0.071+/-0.022 (P<0.01). Referenced to the "true" zero-stress state, the residual strain distribution of different layers in intact rings was shown that the inner surface residual strain was negative at mucosa-submucosa and inner muscle layers and was positive at outer muscle layer, whereas the outer surface residual strain was negative at the mucosa-submucosa layer and positive at the inner and outer muscle layers. For the separated different layered rings, the inner residual strain was negative and outer residual strain was positive; however, the absolute values did not differ (P>0.1). In conclusion, it is possible to microsurgically separate the oesophagus into three layers, i.e., mucosa-submucosa, inner muscle and outer muscle layers, the residual strain differ between the layers, and the residual strain distribution was more uniform after the layers were separated.     

Regional distribution of axial strain and circumferential residual strain in the layered rabbit oesophagus

The oesophagus is subjected to large axial strains in vivo and the zero-stress state is not a closed cylinder but an open circular cylindrical sector. The closed cylinder with no external loads applied is called the no-load state and residual strain is the difference in strain between the no-load state and zero-stress state. To understand oesophageal physiology and pathophysiology, it is necessary to know the distribution of axial strain, the zero-stress state, the stress-strain relations of oesophageal tissue, and the changes of these states and relationships due to biological remodeling of the tissue under stress. This study is addressed to such biomechanical properties in normal rabbits. The oesophagi were marked on the surface in vivo, photographed, excised (in vitro state), photographed again, and sectioned into rings (no-load state) in an organ bath containing calcium-free Kreb's solution with dextran and EGTA added. The rings were cut radially to obtain the zero-stress state for the non-separated wall and further dissected to separate the muscle and submucosa layers. Equilibrium was awaited for 30min in each state and the specimens were photographed in no-load and the zero-stress states. The oesophageal length, circumferences, layer thicknesses and areas, and openings angle were measured from the digitised images. The oesophagus shortened axially by 35% after excision. The in vivo axial strain showed a significant variation with the highest values in the mid-oesophagus (p<0.001). Luminal area, circumferences, and wall and layer thicknesses and areas varied in axial direction (in all tests p<0.05). The residual strain was compressive at the mucosal surface and tensile at the serosal surface. The dissection studies demonstrated shear forces between the two layers in the non-separated wall in the no-load and zero-stress states. In conclusion, our data show significant axial variation in passive morphometric and biomechanical properties of the oesophagus. The oesophagus is a layered composite structure with nonlinear and anisotropic mechanical behaviour.     

四氧嘧啶糖尿病大鼠主动脉零应力状态的变化

目的和方法：将沿径向切开的糖尿病大鼠及对照大鼠主动脉坏分别转正圩Ｋｒｅｂｓ液中,向其中分别加入缩血管物质及舒血管物质达各种浓度;观察其角度变化。用Ｓ－Ｐ法对大鼠主动脉壁肌动蛋白进行染色。结果：四氧嘧啶糖尿病大鼠病程４周时主动脉环展开角显著大于对照（Ｐ〈０．００１）。使用药物后大鼠主动脉坏展开角与使用前相比无明显差异（Ｐ〉０．０５）。糖尿病大鼠主动脉壁肌动蛋白色较对照组明显加深、染色的光密度显著大于     

Effect of Danshen on the Zero-Stress State of Rat's Abdominal Aorta

The objective of our study was to study the effect of danshen, a Chinese herbal medicine known to prevent hypertension, on the zero-stress state of rat's abdominal aorta. The zero-stress state of a blood vessel represents the release of residual stress on the vessel wall, and is the basic configuration of blood vessel affected solely by intrinsic parameters. At the in vivo state, the rat's abdominal aorta was subjected to blood pressure and flow and longitudinal stress. After dissecting from the abdominal aorta, the aortic specimens were cut into small rings at no-load state, in which the internal pressure, external pressure, and longitudinal stress in a short ring-shaped segment were all zero; by cutting radially to release the residual stress in the wall, the vessel ring opened up into a sector quickly, and the sector's configuration would not change at 20 min after cutting and was defined as the zero-stress state of a blood vessel, which was characterized by its residual strain and opening angle. Then aqueous extract of danshen prepared with methanol was added in the Krebs solution, and the changes of the aorta's zero-stress state were monitored by taking photos routinely for analysis to determine the opening angle and residual strain. Additionally, other sets of samples were tested in a Norepinephrine-Krebs solution as positive control or a Krebs solution as negative control, respectively. It was demonstrated that the zero-stress state of rat's abdominal aorta was affected by danshen extract and norepinephrine in two different patterns, while the Krebs solution did not have similar effects. The present work provides a new approach to study the anti-hypertension effect and mechanism of danshen.     

Regional distribution of layer-specific circumferential residual deformations and opening angles in the porcine aorta

Information on the layer-specific residual deformations of aortic tissue and how these vary throughout the vessel is important for understanding the regionally-varying aortic functions and pathophysiology, but not so much can be found in the literature. Toward this end, porcine aortas were sectioned into eighteen rings, with one ring from each anatomical position radially cut to obtain the zero-stress state for the intact wall and the other ring dissected into intimal-medial and adventitial layers; these rings were then radially cut to reach the zero-stress state for the intima-media and adventitia. Peripheral variations in internal/external circumferences, thickness, and opening angle of the intact wall and its layers were measured through image analysis at the no-load and zero-stress states. Intact wall and layer circumferences at both states significantly declined along the aorta, as did intact wall and intimal-medial but not adventitial thickness. Adventitia exhibited the greatest opening angles, approaching 180 deg all over the aorta. The opening angles of the intima-media and intact wall were quite similar, with the highest values in the ascending aorta, the lowest at the diaphragm, and increasing subsequently. Bending-related residual stretches were released by radial cutting that were compressive internally and tensile externally, displaying distinct axial variation for the intima-media and intact wall, and non-significant variation for the adventitia. Evidence is provided for the release upon layer separation of compressive stretches in the intima-media and of tensile stretches in the adventitia, whose values were smallest in the descending thoracic aorta and highest near the iliac artery bifurcation.     

Impact of Age-Dependent Adventitia Inflammation on Structural Alteration of Abdominal Aorta in Hyperlipidemic Mice

Background

The adventitia is suggested to contribute to vascular remodeling; however, the site-selective inflammatory responses in association with the development of atherosclerosis remain to be elucidated.

Methods and Results

Wild-type or apolipoprotein E knockout male C57BL/6J background mice were fed standard chow for 16, 32, and 52 weeks, and the morphology of the aortic arch, descending aorta, and abdominal aorta was compared. Atheromatous plaque formation progressed with age, particularly in the aortic arch and abdominal aorta but not in the descending aorta. In addition, we found that the numbers of macrophages, T-lymphocytes, and microvessels, assessed by anti-F4/80, CD3, and CD31 antibodies, were higher in the adventitia of the abdominal aorta at 52 weeks. These numbers were positively correlated with plaque formation, but negatively correlated with elastin content, resulting in the enlargement of the total vessel area. In aortic tissues, interleukin-6 levels increased in the atheromatous plaque with age, whereas the level of regulated on activation, normal T cell expressed and secreted (RANTES) increased with age, and compared with other sites, it was particularly distributed in inflammatory cells in the adventitia of the abdominal aorta.

Conclusion

This study suggests that adventitial inflammation contributes to the age-dependent structural alterations, and that the activation/inactivation of cytokines/chemokines is involved in the process.     

Biomechanical and morphological properties in rat large intestine

Intestinal stress-strain distributions are important determinants of intestinal function and are determined by the mechanical properties of the intestinal wall, the physiological loading conditions and the zero-stress state of the intestine. In this study the distribution of morphometric measures, residual circumferential strains and stress-strain relationships along the rat large intestine were determined in vitro. Segments from four parts of the large intestine were excised, closed at both ends, and inflated with pressures up to 2kPa. The outer diameter and length were measured. The zero-stress state was obtained by cutting rings of large intestine radially. The geometric configuration at the zero-stress state is of fundamental importance because it is the basic state with respect to which the physical stresses and strains are defined. The outer and inner circumferences, wall thickness and opening angle were measured from digitised images. Subsequently, residual strain and stress-strain distributions were calculated. The wall thickness and wall thickness-to-circumference ratio increased in the distal direction. The opening angle varied between approximately 40 and approximately 125 degrees with the highest values in the beginning of proximal colon (F=1.739, P<0.05). The residual strain at the inner surface was negative indicating that the mucosa-submucosal layers of the large intestine in no-load state are in compression. The four segments showed stress-strain distributions that were exponential. All segments were stiffer in longitudinal direction than in the circumferential direction (P<0.05). The transverse colon seemed stiffest both in the circumferential and longitudinal directions. In conclusion, significant variations were found in morphometric and biomechanical properties along the large intestine. The circumferential residual strains and passive elastic properties must be taken into account in studies of physiological problems in which the stress and strain are important, e.g. large intestinal bolus transport function.     

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.     

Relationship between hypertension, hypertrophy, and opening angle of zero-stress state of arteries following aortic constriction

Examination of changes occurring in the zero-stress state of an organ provides a way to study cellular growth in the organ due to change of physical stresses. The zero-stress state of the aorta is not a tube. It is a sector with an opening angle that varies with the location on the aorta and changes with cellular remodeling. Blood vessel remodeling can be induced by imposing a constriction on the abdominal aorta by a metal clip (aortic banding), which causes an increase of blood pressure, hypertrophy of the aortic wall, and large change of opening angle. The correlation of the opening angle with the blood vessel wall thickness and blood pressure changes in rat's aorta due to aortic banding is presented in this report. The opening angle changes daily following the aortic banding. Blood pressure rises in vessels of the upper body, but that in the lower body decreases at first and then rises to an asymptotic value. Blood vessel wall thickness increases in rough proportion to blood pressure. Vessel diameter changes also. But the most dramatic is the course of change of the zero-stress state. Typically, the time to reach 50 percent of asymptotic hypertrophy of blood vessel wall thickness is about 3-5 days. The corresponding time for blood pressure is about 7 days. The opening angle of the zero-stress state, however, increases rapidly at first, reaches a peak in about 2 to 4 days, then decreases gradually to a reduced asymptote. The exact values of the time constants depend on the location along the aortic tree. In general, the course of change of residual strain is very different from those of the blood pressure and the blood vessel wall thickness.     

Effects of probucol on atherosclerosis of apoE-deficient or LDL receptor-deficient mice.

The effect of probucol on atheroma formation was evaluated using mouse models for atherosclerosis with different diet protocols. Dietary administration of probucol (0.5 %, wt/wt) for 12 weeks reduced total plasma cholesterol levels in both apolipoprotein E (apoE)-deficient mice fed a western diet and in low-density lipoprotein receptor (LDLR)-deficient mice fed a Paigen diet by 60 % and 30 % to 60 %, respectively. Probucol treatment also significantly reduced high-density lipoprotein (HDL) levels in apoE-deficient mice, but not in LDLR-deficient mice. Atherosclerotic plaques in the aortic sinus of probucol-treated apoE-deficient mice were two-fold larger than those in untreated apoE-deficient mice, while the lesions in probucol-treated LDLR-deficient mice were similar to those in untreated LDLR-deficient mice. A strong negative correlation between HDL cholesterol levels and lesion sizes at the aortic sinus was observed in apoE-deficient mice, but not in LDLR-deficient mice. Thus, in contrast to LDLR-deficient mice, probucol had a strong proatherogenic effect in the aortic sinus of apoE-deficient mice associated with the reduction of HDL levels in spite of the reduction of total plasma cholesterol levels. The varying effects of probucol on atherogenesis depend upon the portion of aorta and which animal model is evaluated, implicating that complex cellular events are involved in the effect of probucol.     

Perforin and Granzyme B Have Separate and Distinct Roles during Atherosclerotic Plaque Development in Apolipoprotein E Knockout Mice

The granzyme B/perforincytotoxic pathway is a well established mechanism of initiating target cell apoptosis. Previous studies have suggested a role for the granzyme B/perforin cytotoxic pathway in vulnerable atherosclerotic plaque formation. In the present study, granzyme B deficiency resulted in reduced atherosclerotic plaque development in the descending aortas of apolipoprotein E knockout mice fed a high fat diet for 30 weeks while perforindeficiency resulted in greater reduction in plaque development with significantly less plaque area than granzyme Bdeficient mice. In contrast to the descending aorta, no significant change in plaque size was observed in aortic roots from either granzyme Bdeficient or perforindeficient apolipoprotein E knockout mice. However, atherosclerotic plaques in the aortic roots did exhibit significantly more collagen in granzyme B, but not perforin deficient mice. Together these results suggest significant, yet separate roles for granzyme B and perforin in the pathogenesis of atherosclerosis that go beyond the traditional apoptotic pathway with additional implications in plaque development, stability and remodelling of extracellular matrix.     

Mycoplasma pneumoniae and/or Chlamydophila pneumoniae inoculation causing different aggravations in cholesterol-induced atherosclerosis in apoE KO male mice

Background  

Chamydophila pneumoniae (CP) and/or Mycoplasma pneumoniae (MP) are two bacteria detected in vulnerable atheromas. In this study we aimed to analyze whether CP and/or MP aggravates atherosclerosis induced by cholesterol-enriched diet in C57BL/6 apoE KO male mice. Thirty male apoE KO mice aged eight weeks fed by a diet containing 1% cholesterol until 32 weeks of age were divided into four groups: the first was inoculated with CP (n = 7), the second with MP (n = 12), the third with both CP + MP (n = 5), and the fourth with saline (sham n = 6). The animals were re-inoculated at 36 weeks of age, and sacrificed at 40 weeks of age. Two ascending aorta and one aortic arch segments were sampled. In the most severely obstructed segment, vessel diameter, plaque height, percentage of luminal obstruction and the degree of adventitial inflammation were analyzed. The plaque area/intimal surface ratio was obtained by measuring all three segments. The adventitial inflammation was semiquantified (0 absent, 1 mild, 2 moderate, and 3 diffuse).     

Biomechanical remodelling of obstructed guinea pig jejunum

Data on morphological and biomechanical remodelling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cm H₂O. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner.     

Study on cartilaginous and muscular strains of rat trachea

Han and Fung (1991)[1] studied the zero-stressstates of porcine and canine tracheas by cutting themidpoints of cartilage and muscle respectively. Themethod of Fung, termed Once Cutting method in thispaper, was also used by Liu, Wang and Teng (2002)[2]in studying residual strain of rat tracheas. They all re-ported that the no-load state of trachea is not itszero-stress state, but the residual stress (strain) existsin no-load tracheal ring. The tracheal ring would openup into a figure of “C…     

Study on cartilaginous and muscular strains of rat trachea

This paper introduces a new method, termed Twice Cutting, for obtaining the zero-stress states of cartilage and muscle of trachea. The method applied cuts at the two junctions of tracheal cartilage and muscle perpendicular to the tangent lines of cartilage at its tips. The cartilaginous and muscular opening angles are defined for the first time in Twice Cutting methods. Based on the analysis of cartilaginous and muscular geometric information in no-load and zero-stress states, it is found that there are compressive and tensile residual strains in the inner and outer walls of the cartilage respectively. Residual strains at the muscular inner wall of tracheal rings near bifurcation are negative, whereas those of other rings are positive, and residual strains at outer wall of all rings are positive. This phenomenon of tracheal muscle residual strains is different from those of vessel etc. The results also show that the absolute values of cartilaginous strains are considerably smaller than that of muscular ones, with the ratio being around 0.05. The values of all the tracheal parameters, including residual strains and opening angles, are reducing with the increasing value of tracheal rings’ position. So the consequences obtained in this paper not only indicate that the trachea is a non-uniform tissue along the circumferential and axial directions, but also reveal the differences between the trachea and other living tissues, such as vessel, esophagus. This is a basic research for further work, such as determining stress in trachea, to which the cartilaginous and muscular zero-stress states should be referred.     

Analysis of the strain and stress distribution in the wall of the developing and mature rat aorta

The variation of wall stress distribution with age in the thoracic and abdominal aortas of normotensive rats was studied. Dimensions of the zero-stress configurations were measured at the ages of 4, 8, 12, 20, and 52 weeks. Using data from previously published inflation tests, the circumferential stress-strain relationship was obtained in each age group. The calculated stress distribution showed that the average circumferential stress remained practically constant after the age of 20 weeks. The circumferential stress at the innermost part of the arterial wall was greater than the stress at the outermost part, but the difference was maintained at a moderate level with adjustments in the zero-stress configuration. It is speculated that, after the age of 20 weeks, changes in arterial geometry and rheological properties tend to maintain a constant stress distribution under varying conditions of loading. This distribution was achieved by enhanced growth at the inner part of the media in comparison with the growth at its outer margins and suggests that during development and maturity, the growth of the aorta is modulated by circumferential stress.     

Small intestinal morphometric and biomechanical changes during physiological growth in rats

Changes in small intestinal geometry, residual strain and stress-strain properties during physiological growth were studied in rats ranging from 1 to 32 weeks of age. Small intestinal mass and dimensions increased many-fold with age, e.g. the weight per unit length increased five-fold with age and the wall cross-sectional area increased four-fold. The opening angle of duodenum obtained at zero-stress state was approximately 220 degrees and 290 degrees during the first and second week after birth and decreased to 170 degrees at other ages (p < 0.005). The opening angle of ileum ranged between 120 degrees and 150 degrees . The residual strain of duodenum at the mucosal surface did not vary with age (p > 0.05) whereas the residual strain of ileum at the mucosal surface decreased with age (p < 0.001). The circumferential and longitudinal stress-strain curves fitted well to a mono-exponential function. At a given circumferential stress, the corresponding strain values increased during the first 8 weeks of age (p < 0.05) where after no further change was observed. Hence, the small intestine became more compliant during early life. At a given longitudinal stress, the corresponding strains of ileum and duodenum became larger during the first 2-4 weeks of age (p < 0.05) where after no further change was observed. The small intestine was stiffer in longitudinal direction compared to the circumferential direction. In conclusion, pronounced morphometric and biomechanical changes were observed in the rat small intestine during physiological growth. Such data may prove useful in the understanding of the functional changes of the digestive tract during early life.     

Mechanical properties of elastin along the thoracic aorta in the pig

Understanding the mechanical environment of each component within the arterial wall is fundamental for understanding vascular growth and remodelling and for engineering artificial vascular conduits. We have investigated the mechanical status of arterial elastin by measuring the circumferential mechanical properties of purified elastin as function of position along the descending thoracic aorta of the pig. The tensile circumferential secant modulus, E(sec), measured in uniaxial mechanical tests, increased 30% (P<0.001), from a value of 0.88 MPa in the proximal tissue near the aortic arch to 1.14 MPa in the distal tissue near the diaphragm, indicating the stiffness of the elastin sample increased with position. Breaking stress was 54% higher in the distal tissue compared to the proximal (P<0.001), but the breaking stretch ratio did not change. E(sec) correlated with the ratio of radius to wall thickness measured in the no load state, r(nl)/h(nl), suggesting that the rise in stiffness was linked to ring morphology. The higher stiffness and strength of the distal tissue might be explained by a higher proportion of circumferentially oriented fibres in the distal tissue, which would indicate that the elastin meshwork in the thoracic aorta may become progressively anisotropic with distance from the heart. The ratio r(nl)/(h(nl)E (sec))rose only 7%, which suggests that the in vivo circumferential strain on the elastin may be constant along the pig thoracic aorta. The positional variation in elastin's properties should be taken into account in mechanical studies on purified elastin and in mathematical models of aorta mechanics.     

Effects of mechanical properties and atherosclerotic artery size on biomechanical plaque disruption – Mouse vs. human

Mouse models of atherosclerosis are extensively being used to study the mechanisms of atherosclerotic plaque development and the results are frequently extrapolated to humans. However, major differences have been described between murine and human atherosclerotic lesions and the determination of similarities and differences between these species has been largely addressed recently. This study takes over and extends previous studies performed by our group and related to the biomechanical characterization of both mouse and human atherosclerotic lesions. Its main objective was to determine the distribution and amplitude of mechanical stresses including peak cap stress (PCS) in aortic vessels from atherosclerotic apoE^-/- mice, in order to evaluate whether such biomechanical data would be in accordance with the previously suggested lack of plaque rupture in this model. Successful finite element analysis was performed from the zero-stress configuration of aortic arch sections and mainly indicated (1) the modest role of atherosclerotic lesions in the observed increase in residual parietal stresses in apoE^-/- mouse vessels and (2) the low amplitude of murine PCS as compared to humans. Overall, the results from the present study support the hypothesis that murine biomechanical properties and artery size confer less propensity to rupture for mouse lesions in comparison with those of humans.     

Overexpression of TGF-ß1 in macrophages reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice

Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE^−/− mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice.