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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between atherosclerosis and abdominal aortic aneurysm development is well known. Atherosclerosis cannot explain the whole mechanism. Genetic characters of mechanisms leading to abdominal aortic development is obvious from this study and others. Our study evidences an increased metalloproteases activity in aortic wall proportionally to the size of the abdominal aortic aneurysm. A decrease of aortic wall elastin is evidenced proportionally to the AAA size. Extractable collagen is significantly increased in the aortic wall of patients operated on for aortic rupture.
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PMID:[Mechanism of the growth and rupture of abdominal aortic aneurysm]. 962 40

The objective of this study was to determine the arterial responses to plasma lipid lowering alone or in combination with (1) estrogen replacement therapy or (2) hormone replacement therapy in surgically postmenopausal female monkeys with preexisting atherosclerosis. Eighty-eight female cynomolgus macaques were ovariectomized, fed an atherogenic diet for 24 months, and then assigned by randomized stratification into 4 groups. One group (baseline, n=20) was necropsied at the end of the atherogenic diet period; the remaining 3 groups were fed a plasma lipid-lowering diet (regression) for 30 months. These regression groups were control (diet only), CEE (receiving conjugated equine estrogens alone), and CEE+MPA (receiving CEE and continuous medroxyprogesterone acetate). A previous report described coronary artery functional and histological results; the present report describes biochemical and histological results from the abdominal aorta. Aortic plaque size was not different between groups, similar to previous findings in the coronary arteries. Aortic cholesterol content (milligrams per gram lipid-free dry weight) was lower in the regression groups compared with baseline, both for free cholesterol (mean, control=19.1, CEE=15.7, CEE+MPA=14.4, and baseline=32.7; P<0.001) and for esterified cholesterol (mean, control=18.9, CEE=15.4, CEE+MPA=14.2, and baseline=58.7; P<0.001). This cholesterol efflux could lead to increased plaque stability without changing the physical size of the lesion. Alterations in aortic connective tissue composition were observed in the regression groups. When expressed as a percentage of the lipid-free tissue weight, the aortic elastin content of the control (mean=14.9) and the CEE+MPA (mean=14.0) groups was lower than that of the baseline group (mean=19.0), which was not different from that of the CEE group (mean=15.8). Aortic collagen content, as estimated by hydroxyproline content per milligram of lipid-free tissue, was higher in the control group (mean=67.4) and the CEE+MPA group (mean=66.1) than in the baseline group (mean=56.2; P<0.05). Collagen content of the CEE group (mean=58.9) was not different from that of the baseline group. When the regression groups were considered separately, the aortic collagen content of the CEE group was lower than that of the control group (P<0.05) and tended to be lower than that of the CEE+MPA group (P=0.10), suggesting that CEE therapy (but not CEE+MPA) inhibits potentially detrimental connective tissue alterations that accompany lesion regression. These results have implications for combinations of lipid-lowering and hormone replacement therapies in relation to vascular remodeling and abdominal aortic aneurysm development.
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PMID:Conjugated equine estrogens alone, but not in combination with medroxyprogesterone acetate, inhibit aortic connective tissue remodeling after plasma lipid lowering in female monkeys. 967 78

We analyzed 79 consecutive patients with aneurysms and found a patient who lacked type III collagen. Collagen was extracted from the skin, and the lack of type III collagen was determined by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Only 1 of the 79 patients was found to lack type III collagen. This patient was a 55-year-old man who had sustained an abdominal aortic aneurysm and aortic dissection. He did not show any of the typical clinical symptoms of Ehlers-Danlos syndrome type IV, such as hyperextensible skin and joints. He had none of the usual risk factors nor any clear family history of the syndrome. Furthermore, his collagen fibrils demonstrated a homogeneous appearance. This case may represent a new form of type III collagen deficiency.
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PMID:The lack of type III collagen in a patient with aneurysms and an aortic dissection. 984 62

The objective of the present study was to determine the viscoelastic properties of the common carotid artery in 35 patients with aortic aneurysm before surgery (AAA) (age 71 years, range 61-84), in comparison with 48 patients with essential hypertension (HT: 50 years, range 24-88) and 44 normotensive subjects (NT: 44 years, range 23-85). The second objective was to establish the relations between common carotid artery (CCA) viscoelastic properties and histologic lesions observed on AAA segments, obtained after surgery. CCA diameter was larger and distensibility smaller in AAA patients than in HT and NT. Distensibility of the aortic aneurysm was smaller than that of upstream 'normal' aorta, itself being smaller than control aortas. AAA wall lesions were extensive, associating adventitial and medial fibrosis, elastolysis, smooth muscle rarefaction, neovascularization, inflammation and plaques. The grade of these lesions was not correlated with the mechanical properties of the aorta and CCA; however, they could explain their qualitative alterations. AAA is characterized by severe stiffening and dilatation of large arteries distant from the aneurysm location. Whether this pattern of arterial phenotype is explained by the increase in stiff material (collagen) and the rarefaction of distensible material (smooth muscle and elastin) remains to be determined.
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PMID:[Associations between viscoelastic properties of large arteries and their extracellular matrix composition in abdominal aortic aneurysms in humans]. 1021 30

Abdominal aortic aneurysms (AAAs) represent a chronic degenerative condition associated with a life-threatening risk of rupture. The evolution of AAAs is thought to involve the progressive degradation of aortic wall elastin and collagen, and increased local production of several matrix metallo-proteinases (MMPs) has been implicated in this process. We have previously shown that tetracycline derivatives and other MMP inhibitors suppress aneurysm development in experimental animal models of AAA. Doxycycline also reduces the expression of MMP-2 and MMP-9 by human vascular wall cell types and by AAA tissue explants in vitro. To determine whether this strategy might have a role in the clinical management of small AAA, we examined the effect of doxycycline on aortic wall MMP expression in vivo. Patients were treated with doxycycline (100 mg p.o. bid) for 7 days prior to elective AAA repair, and aneurysm tissues were obtained at the time of surgery (n = 5). Tissues obtained from an equal number of untreated patients with AAA were used for comparison. By reverse transcription-polymerase chain reaction and Southern blot analysis, MMP-2 and MMP-9 were both found to be abundantly expressed in the aneurysm wall. Preoperative treatment with doxycycline was associated with a 3-fold reduction in aortic wall expression of MMP-2 and a 4-fold reduction in MMP-9 (p < 0.05 compared to untreated AAA). These preliminary results suggest that even short-term treatment with doxycycline can suppress MMP expression within human AAA tissues. Given its pleiotropic effects as an MMP inhibitor, doxycycline may be particularly effective in suppressing aortic wall connective tissue degradation. While it remains to be determined whether MMP inhibition will have a clinically significant impact on aneurysm expansion, it is expected that this question can be resolved by a properly designed prospective randomized clinical trial.
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PMID:MMP inhibition in abdominal aortic aneurysms. Rationale for a prospective randomized clinical trial. 1041 28

The optimal surgical procedure for severe renal secondary hyperparathyroidism (sHPT) is still a point of controversy. Total parathyroidectomy (PTX) without auto-transplantation was abandoned for fear of an adynamic bone condition; however, in the case of autotransplantation recurrent sHPT is frequent and promotes atherosclerosis. We studied 11 hemodialysis patients (age 59+/-12 years) on dialysis for 18 (12-30) years in whom total PTX was performed due to severe sHPT (group I; intact PTH: 1,240+/-230 pg/ml), and 5 patients (age 55+/-10 years) without renal insufficiency who inadvertently received total PTX during thyroid surgery (group II). After total PTX (group I, 26+/-18 [9-59] months; group II, 252+/-188 [22 480] months) both groups showed no measurable intact PTH levels. Calcium homeostasis was maintained by oral substitution with calcium (group I, calcium dialysate of 2.0 mmol/l), vitamin D and calcitriol (serum parameters in groups I and II: calcium 2.4 and 2.2 mmol/l; phosphate 1.8 and 1.1 mmol/l; 25(OH)-vitamin D(3) 21 and 34 ng/ml; 1,25(OH)(2)-vitamin D(3) 32 and 41 pg/ml, respectively). In group I, after total PTX there was a rapid and sustained improvement in bone pain with markedly enhanced physical activity and endurance. High turnover osteopathy markedly improved as indicated by declining levels of native osteocalcin (90+/-17 vs. 26+/-18 ng/ml), bone alkaline phosphatase (74+/-12 vs. 12+/-6 ng/ml), and carboxyterminal cross-linked telopeptide of type-I collagen (65+/-16 vs. 40+/-21 ng/ml) but increasing levels of carboxyterminal propeptide of type-I procollagen (120+/-36 vs. 148+/-41 ng/ml). Recalcification of bone was excellent as demonstrated by X-ray and confirmed by bone histology. Itching extravascular calcific deposits and calcifications of blood vessel and cardiac valves immediately stopped after total PTX. Moreover, 6 sHPT patients suffered from severe atherosclerotic lesions such as thoracic aortic aneurysm (n = 3) or abdominal aortic aneurysm (n = 3) which showed size progression before but not after total PTX when annually controlled by ultrasonography. In group II, even long after total PTX, there was no clinical, radiological, histological or biochemical evidence for low turnover osteopathy. In conclusion, our data indicate that substitution with vitamin D(3) metabolites and calcium can prevent deleterious bone effects of hypoparathyroidism in hemodialysis patients and in patients with normal kidney function and may compensate for the missing PTH action. Over this, a better survival rate is expected as a consequence of the beneficial effect of total PTX on the progression of atherosclerotic lesions. We suggest reconsideration of total PTX without autotransplantation in dialysis patients with severe sHPT who are not eligible for renal transplantation.
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PMID:Long-term results of total parathyroidectomy without autotransplantation in patients with and without renal failure. 1043 1

Background: In our previous canine model of abdominal aortic aneurysm, although aneurysm growth was observed, the aneurysms did not rupture. This prompted us to develop a swine model, which has the advantage of fibrinolytic and coagulation systems similar to those found in humans. Methods: We simulated aneurysms by connecting fascia pouches to the aorta. In nine pigs, two pieces of fascia (5 x 8 cm each) were sutured to the posterior surface of the aorta. After the lateral edges of the aorta were sutured together, the aorta was clamped below the renal arteries and at the aortic bifurcation. We then resected a piece of aorta within the pouch, clamped the pouch below the open roof, and unclamped the aorta. When the entire pouch had been sutured, the last clamp was removed and blood flowed into the "aneurysm." The total aortic cross clamp time was between 4 and 25 minutes. Results: "Aneurysm" size ranged from 3.0 x 2.5 cm to 7.5 x 4.0 cm (length x width). Aneury sm rupture occurred in seven pigs between 4 and 43 days after initial surgery; however, rupture never occurred at a suture site. Aneurysm size at rupture was two to four times greater than that of the original pouch. We found thrombus in all of the aneurysms examined more than 2 days after surgery. Histology revealed aneurysm walls that were thicker than the fascia. Although fascia segments could be identified because of their characteristic trilayer of thick collagen fibers, most of the aneurysm wall contained thin collagen fibers. These observations are consistent with new collagen production. Conclusion: We constructed a swine model of abdominal aortic aneurysm that possessed the features of growth and rupture necessary to simulate human aneurysms. Our method will allow techniques designed to isolate aneurysms from the circulation to be tested in a model with a fibrinolytic system similar to that of humans.
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PMID:Spontaneous Rupture and Thrombotic Effects in a Swine Model of Untreated Abdominal Aortic Aneurysms. 1061 82

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.
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PMID:Circulating biochemical marker levels of collagen metabolism are abnormal in patients with abdominal aortic aneurysm. 1082 55

Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.
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PMID:Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms. 1134 73

Abdominal aortic aneurysm is a smoking-related disorder. Cadmium, inhaled from cigarettes, may accumulate in the aorta and facilitate weakening of the aorta through adverse effects on smooth muscle cell metabolism. Cadmium was measured by atomic absorption spectrometry in infrarenal aortas from 13 patients with abdominal aortic aneurysm and from 17 age- and sex-matched patients with normal-diameter abdominal aorta. Total cadmium content was associated with smoking, assessed as pack-years (r=0.54, P=0.004), but was similar in aneurysmal and undilated aortas. The cadmium content (mean+/-SE) was higher in the media (3.25+/-0.53 ng/mg dry wt, 7+/-1.2 micromol/L) than in the intima or adventitia (1.14+/-0.24 and 1.87+/-0.38 ng/mg dry wt, respectively; ANOVA, P<0.005). There was a strong correlation between medial cadmium content and pack-years of smoking (r=0.87, P<0.001). In aortic smooth muscle cells cultured on fibrillar collagen, cadmium inhibited DNA synthesis and collagen synthesis and diminished cell numbers (IC(50) 2 micromol/L, 6 micromol/L, and 6 micromol/L, respectively), but higher concentrations of cadmium were required for upregulation of metallothionein (EC(50) 23 micromol/L). The cadmium content of the aorta increases in direct proportion to the pack-years of cigarettes smoked, with selective accumulation in the medial layer. However, the cadmium content of aneurysmal aortas was not higher than that of nondilated aortas for patients with matched smoking history. In smokers, the level of cadmium accumulation is probably sufficient to impair the viability of cultured smooth muscle cells. Similar mechanisms could underlie the development of degenerative aortic disease in smokers.
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PMID:Cadmium accumulation in aortas of smokers. 1134 88


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