Abdominal aortic aneurysms are associated with altered matrix proteins of the nonaneurysmal aortic segments

Purpose: Abdominal aortic aneurysms (AAA) are associated with diffuse arteriomegaly and peripheral aneurysms, suggesting a generalized process. Elastin and collagen are the key structural proteins of the aorta, and their relative content is markedly altered in tissue from AAA. Our purpose was to investigate elastin and collagen content in the proximal, nonaneurysmal segments of aortas with infrarenal AAA.Methods: After extraction of lipid, calcium, and soluble proteins, hydroxyproline (collagen) and desmosine-isodesmosine (elastin) contents were determined by high-performance liquid chromatography in the ascending and descending thoracic, supraceliac, and suprarenal aorta. By repeated measures of analysis of covariance, collagen was found to be increased throughout the aorta in AAA as compared with normal aorta or aorta with atherosclerotic occlusive disease. This difference remained significant when adjustments were made for group differences in age and degree of atherosclerosis. This increase in collagen content results in a dilutional decrease in elastin concentration. These data demonstrate that the same matrix protein alterations found in AAA tissue occur throughout the aorta, differing only in magnitude in the aneurysmal and nonaneurysmal segments. These data suggest that aneurysm formation may relate to alterations in the regulation of elastin and collagen. (J VASC SURG 1994;19:797-803.)     

Collagen in abdominal aortic aneurysm: typing, content, and degradation

The collagen content of the media of infrarenal aorta has been compared in age- and sex-matched normal aorta and dilated and nondilated atherosclerotic aorta. The proportion of collagen was increased in aneurysmal aorta from 62% to 84% and appears to be the result of preferential elastin degradation. The ratio of type I to type III collagen, estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis of specific cyanogenbromide peptides, did not vary significantly from 2:1 in any of the three groups of aortas. There was no evidence of increased collagenase activity in unruptured aneurysmal aorta. Collagenase activity was increased in ruptured aneurysmal aorta but could only be satisfactorily measured after resolution from the endogenous tissue inhibitor of metalloproteinases. We suggest that only limited collagen turnover occurs in the media of abdominal aortic aneurysms before rupture. A subgroup of three patients with a significant family history of aneurysm had lower amounts of type III collagen in the aortic media, suggesting that abnormalities in type III collagen may be one of the genetic factors contributing to familial clustering of aneurysms.     

Thoracic and abdominal aortic dimension in 70-year-old men and women--a population-based whole-body magnetic resonance imaging (MRI) study

OBJECTIVE: The aim of this population-based study was to determine the optimal dividing-line between normal aorta and aneurysm for different aortic segments in 70-year-old men and women by means of whole-body magnetic resonance imaging. METHODS: Two hundred thirty-one subjects (116 men), randomly recruited from a population-based cohort study, were included. The smallest outer diameter (dia) was measured on the axial survey scan on six predefined aortic segments: (1) ascending aorta, (2) descending aorta, (3) supraceliac aorta, (4) suprarenal aorta, (5) largest infrarenal abdominal aorta, and (6) aortic bifurcation. Relative aortic dia were calculated by dividing a given aortic dia by the suprarenal aortic dia. The dividing-line between normal aorta and aneurysm at different aortic segments was estimated by taking the mean dia +2 SD and/or mean ratio of the aortic segment to the suprarenal aorta +2 SD. RESULTS: The mean dia of the six segments were 4.0 cm (SD 0.4), 3.2 cm (0.3), 3.0 cm (0.3), 2.8 cm (0.3), 2.4 cm (0.5), and 2.3 cm (0.3) in men. The corresponding dia in women were 3.4 cm (0.4), 2.8 cm (0.3), 2.7 cm (0.3), 2.7 cm (0.3), 2.2 cm (0.3), and 2.0 cm (0.2). The mean ratio to the suprarenal aorta was 1.4 (SD 0.2) for the ascending aorta, 1.2 (0.1) for the descending aorta, and 0.9 (0.2) for the infrarenal aorta in men. The corresponding ratios in women were 1.3 (0.2), 1.0 (0.1), and 0.8 (0.1). CONCLUSION: For men the suggested dividing-line (dia and ratio) between normal aorta and aneurysm for the ascending aorta is 4.7 cm dia and 1.8 ratio, for the descending aorta 3.7 cm dia and 1.5 ratio, and for the infrarenal aorta is 3.0 cm dia and 1.1 ratio. The corresponding dividing-lines for women are 4.2 cm dia and 1.7 ratio, 3.3 cm dia and 1.3 ratio, and 2.7 cm dia and 1.0 ratio.     

大鼠异种腹主动脉移植形态学重构

目的：研究免疫排斥反应诱导移植血管损伤与重构的形态变化特征以及与腹主动脉瘤的关系。方法：选取豚鼠SD大鼠腹主动脉瘤模型．采用血管特殊染色及计算机图像半定量分析技术，分别于术后1、2、3、4周动态观测和比较移植腹主动脉平滑肌、弹力蛋白和胶原蛋白相对含量、内外径以及腔面积的变化。结果：术后移植腹主动脉各形态学指标均呈渐进性变化，其中术后1周平滑肌及胶原蛋白已明显减少，外径也明显增大；弹力蛋白于术后1周出现减少，至第2周已达最高峰；而内径以及腔面积于术后1周反而减少，3周后才明显增大。并且，弹力蛋白、平滑肌减少与腹主动脉扩张呈现显负相关。结论：异种腹主动脉移植结构重构以平滑肌反应最敏感，弹力蛋白和外径变化最显。可导致腹主动脉呈瘤样扩张。     

The role of type I collagen in aortic wall strength with a homotrimeric

PURPOSE: Elastin and collagen (types I and III) are the primary load-bearing elements in aortic tissue. Deficiencies and derangements in elastin and type III collagen have been associated with the development of aneurysmal disease. However, the role of type I collagen is less well defined. The purpose of this study was to define the role of type I collagen in maintaining biomechanical integrity in the thoracic aorta, with a mouse model that produces homotrimeric type I collagen [alpha1(I)]3, rather than the normally present heterotrimeric [alpha1(I)]2 alpha2(I) type I collagen isotype. METHODS: Ascending and descending thoracic aortas from homozygous (oim/oim ), heterozygous (oim /+), and wildtype (+/+) mice were harvested. Circumferential and longitudinal load-extension curves were used as a means of determining maximum breaking strength (Fmax) and incremental elastic modulus (IEM). Histologic analyses and hydroxyproline assays were performed as a means of determining collagen organization and content. RESULTS: Circumferentially, the ascending and descending aortas of oim /oim mice demonstrated significantly reduced Fmax, with an Fmax of only 60% and 23%, respectively, of wildtype mice aortas. Oim/oim descending aortas demonstrated significantly greater compliance (decreased IEM), and the ascending aortas also exhibited a trend toward increased compliance. Reduced breaking strength was also demonstrated with longitudinal extension of the descending aorta. CONCLUSION: The presence of homotrimeric type I collagen isotype (absence of alpha2(I) collagen) significantly weakens the aorta. This study demonstrates the integral role of type I collagen in the biomechanical and functional properties of the aorta and may help to elucidate the role of collagen in the development of aneurysmal aortic disease or dissection.     

The effect of suprarenal cross-clamping on abdominal aortic aneurysm repair.

Two hundred five patients who underwent elective abdominal aortic aneurysm repair were divided into two groups: those who underwent infrarenal cross-clamping alone (n = 166) and those who underwent suprarenal cross-clamping alone or combined with infrarenal cross-clamping (n = 39). Mortality was comparable between groups (1.2% for infrarenal cross-clamping vs 2.6% for suprarenal cross-clamping). Transient renal insufficiency was more frequent in the suprarenal group than in the infrarenal group (28% vs 10%), but dialysis rates (3% for suprarenal vs 2% for infrarenal) were similar. Cardiac morbidity was comparable between groups as well. Operating room data reflected the technical challenge of complex aneurysm repairs. The retroperitoneal approach was the preferred exposure in the suprarenal group since better access to the suprarenal aorta may be achieved with this technique. While abdominal aortic aneurysm repairs requiring suprarenal cross-clamping remain a technical challenge, the risks are not formidable and suprarenal cross-clamping should be considered when confronted with difficult periaortic dissection.     

Smooth muscle cell apoptosis in aneurysmal,occlusive, and normal human aorta

Purpose: Apoptosis is a universal physiologic mechanism of cell death that regulates mass and architecture in many tissues. Recently, apoptosis has been described as a feature in human vascular atherosclerosis and large-vessel structural integrity. To dissect mechanisms of aortic disease, we determined the extent of smooth muscle cell (SMC) apoptosis in aneurysmal, occlusive, and normal human aortic tissue.Methods: Tissue samples of aneurysmal, occlusive, and normal human infrarenal aorta were evaluated. DNA fragmentation detection methods and standard immunohistochemical techniques were used to determine apoptosis and SMC density in the medial layer of aortas. Apoptotic cells and SMC nuclei were counted by means of computer-generated image analysis. The results of all aortic subtypes were compared statistically by analysis of variance.Results: The samples evaluated were 16 aneurysmal, 6 occlusive, and 5 normal human aortas. α₁-Actin immunostaining confirmed the predominance of SMC to the medial layer of all aortic samples. The SMC density was greatest within normal aortas with 291.0 ± 86.9 cells per high-powerfield (hpf) compared with occlusive aorta with 278.21 ± 117.7 cells per hpf (p = .43) and aneurysmal aorta with 271.76 ± 90.6 cells per hpf (p = .36). Correspondingly, apoptosis of SMCs was greatest within aneurysmal aortas, with 12.13 ± 11.0 cells per hpf compared with occlusive aortas with 1.29 ± 2.0 cells per hpf (p = .0007) and normal aortas with 3.75 ± 4.6 cells per hpf (p = .01).Conclusion: Apoptosis of SMCs is increased and SMC density is decreased within the medial layer of aneurysmal aortic tissue as compared with normal and occlusive aortas. Structural degeneration of aortic tissue at the cellular level contributes to aneurysm formation.     

支架型人工血管临床应用的初步经验

目的探讨支架型人工血管治疗各类动脉瘤的临床效果。方法本组包括夹层动脉瘤 4 8例 ;腹主动脉瘤 13例 ;降主动脉、左锁骨下动脉、肾下和肾上腹主动脉假性动脉瘤分别为 4例、1例、2例和 1例 ;左、右髂动脉瘤各 1例。对夹层动脉瘤和假性动脉瘤均行破口封堵术 ,真性腹主动脉瘤行隔绝术。结果本组均获技术成功。围手术期死亡 2例。 5例夹层动脉瘤术后近侧有少量残余漏 ,但 4例半年后近侧渗漏消失 ,9例残存远侧破口少量返流。腹主动脉瘤 6例术后即时有轻度内漏 ,3个月后 5例内漏消失。结论支架型人工血管治疗夹层动脉瘤、假性动脉瘤和真性动脉瘤手术微创、安全 ,但其远期疗效需进一步观察。     

Rapamycin suppresses experimental aortic aneurysm growth

OBJECTIVE: Inflammatory modulators are important in the pathogenesis of aneurysmal disease. Gene expression profiling of experimental abdominal aortic aneurysm (AAA) tissue demonstrated upregulation of the FK506BP12 (rapamycin binding protein) gene product. Rapamycin is a potent immunosuppressor that prevents recurrent stenosis. However, its effect on aneurysm formation has not been studied. We therefore examined the effect of rapamycin in an experimental rat AAA model. METHODS: Adult male Wistar rats underwent elastase infusion into isolated infrarenal aortas to create experimental aneurysms. Rats were randomized to receive either rapamycin or placebo via gastric lavage daily starting on the day of surgery. On postoperative day 7 the aneurysm was measured, the infrarenal aorta was harvested, and the rats were euthanized. NF kappa B was measured with Western blotting as a marker of inflammation. Matrix metalloproteinase (MMP)-9 protein levels were measured. Hematoxylin-eosin and elastin staining were used to examine tissue inflammation and elastin preservation. RESULTS: Aneurysms were significantly smaller in diameter in the rapamycin-treated group (3.3 +/- 0.7 mm vs 4.5 +/- 0.5 mm; P <.0001). NF kappa B levels were significantly reduced by 64% +/- 14% in rapamycin-treated aortas (P =.023). MMP-9 was reduced in rapamycin-treated aortas by 54% +/- 22% (P =.043). Hematoxylin-eosin and elastin staining showed no changes in inflammatory infiltrate or degradation of elastin fibers in elastase-infused aortic segments in rapamycin-treated rats. CONCLUSION: Rapamycin significantly reduces the rate of aneurysm expansion in the experimental AAA rat model by 40%. Biochemical evidence suggests that this is related to suppression of inflammatory signaling and decreased MMP-9 levels. Rapamycin could provide a new treatment for small aneurysms. CLINICAL RELEVANCE: Human aortic aneurysms are characterized histologically by an inflammatory infiltrate with severe proteolytic destruction. Rapamycin is an immunosuppressive agent commonly used to control transplant rejection and intimal hyperplasia by modulating the inflammatory cascade. In this experimental model rapamycin suppressed aneurysm expansion, decreased NF kappa B activation (a marker of inflammation), and decreased matrix metalloproteinase-9 levels. It is hoped that rapamycin or other similar anti-inflammatory drugs will one day be able to control aneurysm expansion in patients     

Acute and chronic dissections of the abdominal aorta: clinical features and treatment

We report seven cases of dissection of the abdominal aorta. Three patients had acute back pain, whereas four patients had more chronic courses. In six cases, as a result of the palpation of a pulsatile abdominal mass, clinical diagnosis was an atheromatous aneurysm. Angiography and CT scanning demonstrated a dissected abdominal aorta and a normal thoracic aorta. Six patients with an infrarenal dissection were treated by replacement of the aorta with a Dacron prothesis, and one patient with an suprarenal dissection was treated conservatively. With a mean follow-up of 3 years, all patients were alive and free of symptoms. These results favor graft replacement in case of infrarenal aortic dissection and more selective surgical indications in suprarenal aortic dissection.     

Collagen types and matrix protein content in human abdominal aortic aneurysms

Deficiencies of total collagen, type III collagen, and elastin have been proposed to explain aneurysm formation. Infrarenal aortas were collected from 19 patients (age 70 +/- 7 years) undergoing operative repair of abdominal aortic aneurysms (diameter 7 +/- 2 cm) and from 13 autopsies (age 63 +/- 17 years) of patients without aneurysm disease (controls). Wall thickness and collagen and elastin concentration were determined in full-thickness aorta. Collagen types I and III were measured after digestion with cyanogen bromide, which solubilized nearly 90% of total collagen for typing. Cyanogen bromide peptides were separated by sequential carboxymethylcellulose and agarose chromatography and quantified by peak area measurement with computerized image analysis. Histologic examination revealed prominent inflammatory cell infiltration and deficient, fragmented elastin in the aneurysms. Aortic wall thickness was similar in aneurysms and in control specimens. In the aneurysms, collagen was increased (37% +/- 16% vs 24% +/- 5%; p less than 0.05) and elastin was decreased (1% +/- 1% vs 12% +/- 7%; p less than 0.001), expressed as a percentage of delipidized, decalcified dry weight. Collagen type I accounted for 74% +/- 4% of aneurysm and 73% +/- 4% of control collagen solubilized for typing, and collagen type III accounted for 26% +/- 4% of aneurysm and 27% +/- 4% of control collagen solubilized for typing. Neither patients with a family history of aneurysms nor those without a history of aneurysms had collagen type III deficiency. Atherosclerotic abdominal aortic aneurysms are associated with an inflammatory process and may result from elastin degradation and not a deficiency of type III collagen.     

Integrins and extracellular matrix proteins in the human childhood and adolescent growth plate

Interaction of chondrocytes with the surrounding matrix significantly influences differentiation and growth. These processes involve cell surface proteins, particularly integrins. The aim of this study was to compare the expression of integrins (alpha1, alpha2, alpha3, alpha5, alpha6, alphav, beta1, beta3, and beta5 subunits) together with matching binding proteins in human childhood and adolescent growth plate cartilage using immunohistochemistry. Integrin beta1 was detected in all chondrocytes of the growth plate cartilage, beta3 only in osteoclasts of the opening zone, and beta5 in hypertrophic chondrocytes and osteoblasts. Integrin alpha1, alpha2, and alpha5 subunits were expressed by chondrocytes in the proliferative and hypertrophic zone as well as in osteoblasts and osteoclasts. Integrin av and alpha6 subunits were present in chondrocytes of all zones, alpha3 only in osteoclasts. Collagen type II and fibronectin were seen throughout the growth plate, collagen type X in the hypertrophic zone, collagen type I in the ossifying trabecules. Laminin was expressed by chondrocytes in the resting zone and more weakly in the proliferative zone, collagen VI was present in the pericellular and interterritorial matrix in all zones of the growth plate. These results differ from previous reports on the distribution of integrins in the fetal growth plate. However, there was no difference in integrin expression in children before and during puberty. Our results indicate that integrin expression is not influenced by endocrine factors during sexual maturation and suggest that the process of skeletal maturation is not regulated via altered integrin expression.     

Alteration of Elastin, Collagen and their Cross-links in Abdominal Aortic Aneurysms

OBJECTIVES: although the mechanism of arterial dilation and aneurysm development has not been clarified, the degradation of elastin and collagen plays undoubtedly a critical role. We evaluated the elastin and collagen content through the detection of their cross-links in aneurysmal and non-aneurysmal abdominal aortic walls. MATERIALS AND METHODS: in 26 human abdominal aortic aneurysm specimens obtained during surgery and in 24 autopsy control samples of non-aneurysmal abdominal aorta the tissue content of elastin and collagen cross-links were measured by HPLC. Collagen was also detected by evaluating two characteristic amino acids, 4-hydroxyproline (4-hypro) with a colorimetric method and 5-hydroxylysine (5-hylys) by gas chromatography. RESULTS: significantly fewer elastin cross-links were found in aneurysm samples compared to controls (desmosines and isodesmosines: 90% reduction; p<0.01). The opposite was true for pyridinoline collagen cross-links (350% increase) and deoxypyridinolines (100% increase, p=0.01). Tissue content of 5-hylys, 4-hypro and total amino acids were reduced significantly by 50% in aneurysmal samples. CONCLUSIONS: beside confirming decreased elastin content in aneurysmal walls, these results show a concurrent increase of collagen cross-links. Since total collagen markers were decreased (decreased 4-hypro and 5-hylys) it is reasonable to suggest that in aneurysmal aortic walls old collagen accumulates cross-links while new collagen biosynthesis is somehow defective.     

Vascular smooth muscle cell apoptosis in aneurysmal, occlusive, and normal human aortas

PURPOSE: Apoptosis is a physiologic mechanism of cell death that regulates mass and architecture in many tissues. Apoptosis has been described as a feature in human vascular atherosclerosis and large vessel structural integrity. We examined the extent of vascular smooth muscle cell (VSMC) apoptosis in aneurysmal, occlusive, and normal human aortic tissue. METHODS: Tissue samples of aneurysmal, occlusive, and normal human infrarenal aorta were evaluated. DNA fragmentation detection methods, immunohistochemistry, and DNA electrophoresis determined VSMC density, VSMC apoptosis, and apoptosis markers. Apoptotic cells and VSMC nuclei were counted with the use of computer-generated image analysis. Aortic subtypes were compared statistically by analysis of variance. RESULTS: Seventeen aneurysmal, ten occlusive, and five normal human aortas were evaluated. By alpha(1)-actin immunostaining, VSMC density was least in aneurysmal aortas (271.8 +/- 13.5 cells/high-power field [HPF]) compared with occlusive aorta (278.2 +/- 39.4 cells/HPF) and normal aortas (291.0 +/- 25.4 cells/HPF; P = not significant). Presence of apoptotic VSMCs was demonstrated by terminal deoxynucleotidyl transferase fragment end labeling and propidium iodide nuclear staining. VSMC apoptosis was greatest within aneurysmal aortas with 11.7 +/- 1.5 cells/HPF compared with occlusive aortas with 3.3 +/- 0. 8 cells/HPF (P <.05) and normal aortas with 3.75 +/- 4.6 cells/HPF (P <.05). Significant differences in apoptosis markers, p53 or bcl-2, could not be demonstrated by immunohistochemistry or DNA electrophoresis in aortic subtypes. CONCLUSION: Apoptosis of VSMCs is increased and VSMC density is decreased within the medial layer of aneurysmal aortic tissue. Structural degeneration of aortic tissue at the cellular level contributes to aneurysmal formation.     

Effect of impaired vasa vasorum flow on the structure and mechanics of the thoracic aorta: implications for the pathogenesis of aortic dissection.

OBJECTIVE: To investigate the alterations of structure and mechanical properties of the aortic wall, resulting from impairment of vasa vasorum flow. METHODS: Eight healthy Landrace pigs were subjected to interruption of vasa vasorum flow to the upper segment of their descending thoracic aorta. Under sterile conditions, the periaortic tissue was excised and the contiguous intercostal arteries were ligated. Ten sham-operated pigs were used as controls. Fifteen days postoperatively, the animals were sacrificed and their upper descending thoracic aortas were removed. Histology, and collagen and elastin content determination by image analysis technique were performed. Mechanical analysis of aortic strips was carried out with a uniaxial tension device and stress-strain curves were obtained. RESULTS: In contrast to normal aortic walls of the control group, histology of the avascular aortas revealed severe ischemic necrosis of the outer media along with abnormal straightening of the elastin and collagen fibers, without significant collagen and elastin content changes. The borderline between the outer ischemic and inner non-ischemic media was sharp, and an outset of dissection was observed at this point. Mechanical analysis showed that at the same level of strain, the ischemic aorta was significantly stiffer at both low (P=0.03) and high strains (P=0. 003). CONCLUSIONS: Impairment of blood supply to the thoracic aorta leads to abnormal morphology of elastin and collagen fibers of the outer media, resulting in increased aortic stiffness under a wide range of stresses. In the clinical setting, decreased vasa vasorum flow, reportedly occurring in arterial hypertension, may increase the stiffness of the outer media of the thoracic aorta and produce interlaminar shear stresses, contributing to the development of aortic dissection.     

Endovascular Repair of a ruptured abdominal aortic and iliac artery aneurysm with an acute iliocaval fistula secondary to lymphoma

Abdominal aortic aneurysms (AAA) are common and generally asymptomatic unless rupture occurs. A 3 to 4-cm AAA has a 1-2% risk of rupture over 5 years. We present the case of an 85-year-old male with a history of chronic lymphocytic leukemia, a 3-cm infrarenal AAA, and a 2-cm right common iliac artery aneurysm whose AAA ruptured and who developed an acute iliac artery–to–vena cava fistula secondary to eroding adenopathy from an aggressive low-grade lymphoma. Initially, an open repair was attempted but access to the aorta was not possible because of complete encasement of the infrarenal and suprarenal aorta with tumor that was clinically invading the aortic wall. Secondary tumor invasion into the aorta is a rare complication. An endovascular repair was accomplished with successful exclusion of both the aneurysm and the iliocaval fistula. Endovascular repair provides a valuable alternative in the "hostile abdomen" when standard open repair may be hazardous or impossible.     

Interleukin-1ß induces differential gene expression in aortic smooth muscle cells*

Purpose: Abdominal aortic aneurysms are characterized by an accelerated turnover of extracellular matrix proteins and by an inflammatory infiltrate that releases the cytokines interleukin-1ß and tumor necrosis factor-α. We examined the gene expression of human aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells after treatment with interleukin-1ß and tumor necrosis factor-α by measuring the changes in smooth muscle cell collagen, elastin, collagenase, and tissue inhibitor of metalloproteinase messenger ribonucleic acid levels in response to these cytokines.Methods: Biopsy of aneurysmal aorta (n = 6) and donor normal aorta (n = 3) was obtained at operation. Medial smooth muscle cells were cultured, passaged (P2 to P4), and incubated with 0, 10, 100, or 1000 pg/ml interleukin-1ß, tumor necrosis factor-α, or platelet-derived growth factor for 24 hours. Total ribonucleic acid was harvested. Percentage changes in messenger ribonucleic acid from control levels for type I and type III procollagen, elastin, collagenase, 72 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 were measured by Northern hybridization. Analyses were performed with analysis of variance (p < 0.05). All comparisons between aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells represent comparisons between one aneurysmal aorta and one normal aorta.Results: Added interleukin-1ß resulted in significant, dose-dependent increases in the collagenase messenger ribonucleic acid level at all concentrations tested in both aneurysmal aorta and normal aorta. The increase in the collagenase messenger ribonucleic acid level ranged from a minimum increase of 123% for 10 pg/ml interleukin-1ß in aneurysmal aortic smooth muscle cells to a maximum of 450% for 1000 pg/ml interleukin-1ß in normal aortic smooth muscle cells. Interleukin-1ß caused a significant decrease in the steady-state messenger ribonucleic acid levels for type 1 procollagen in both aneurysmal and normal aorta. The greatest reduction in type 1 procollagen messenger ribonucleic acid levels occurred at 100 pg/ml interleukin-1ß in both aneurysmal aortic smooth muscle cells (–39%) and normal aortic smooth muscle cells (–48%). The only observed qualitative difference between aneurysmal aortic smooth muscle cells and normal aortic smooth muscle cells was the change in tissue inhibitor of metalloproteinase-1 messenger ribonucleic acid levels in response to added interleukin-1ß. In aneurysmal aortic smooth muscle cells interleukin-1ß at 1000 pg/ml significantly increased messenger ribonucleic acid levels by 82%, whereas levels of tissue inhibitor of metalloproteinase-1 messenger ribonucleic acid in normal aortic smooth muscle cells did not change in response to added interleukin-1ß. Interleukin-1ß did not alter messenger ribonucleic acid levels for type III procollagen, elastin, type IV collagenase, or tissue inhibitor of metalloproteinase-2 in aneurysmal aorta or normal aorta. When tumor necrosis factor-α or platelet-derived growth factor were added, this did not significantly change aneurysmal aortic smooth muscle cells messenger ribonucleic acid levels for collagenase, type IV collagenase, tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2, and type I and type III procollagen. Conclusions: These findings suggest that interleukin-1ß, through its effect on smooth muscle cell collagenase and collagen gene expression, mediates the increased matrix turnover observed in aneurysms. Macrophages may induce changes in aortic smooth muscle cell gene expression in a paracrine manner that could lead to aneurysm formation. (J VASC SURG 1994;20:774-86.)