Background-Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. Methods and Results-We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6.We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the Ϫ174 G3 C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, Pϭ0.01). In 466 patients with small aneurysms, the frequency of the Ϫ174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis Pϭ0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), Pϭ0.036, and 0.51 (95% CI 0.25 to 1.00), Pϭ0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. Conclusions-Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the Ϫ174 G3 C IL-6 genotype predicts future cardiovascular mortality.
Abstract-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 (rϭ0.54, Pϭ0.004), but was similar in aneurysmal and undilated aortas. The cadmium content (meanϮSE) was higher in the media (3.25Ϯ0.53 ng/mg dry wt, 7Ϯ1.2 mol/L) than in the intima or adventitia (1.14Ϯ0.24 and 1.87Ϯ0.38 ng/mg dry wt, respectively; ANOVA, PϽ0.005). There was a strong correlation between medial cadmium content and pack-years of smoking (rϭ0.87, PϽ0.001). In aortic smooth muscle cells cultured on fibrillar collagen, cadmium inhibited DNA synthesis and collagen synthesis and diminished cell numbers (IC 50 2 mol/L, 6 mol/L, and 6 mol/L, respectively), but higher concentrations of cadmium were required for upregulation of metallothionein (EC 50 23 mol/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. Key Words: aortas Ⅲ aneurysm Ⅲ smoking Ⅲ muscle smooth Ⅲ collagen C admium is one of the many toxic components of inhaled tobacco smoke. The amount of cadmium inhaled from each pack of 20 cigarettes is Ϸ16 g. 1 Cadmium has a long elimination time (estimated at 10 to 30 years), providing the possibility for the accumulation of substantial amounts of cadmium during the lifetime of a smoker. There are reports that cadmium alters the metabolism of cultured human aortic smooth muscle cells and the processing of collagen. 2,3 Cadmium also blocks calcium channels and inhibits ATPases and other ion transport systems.Smoking is the most consistent risk factor for the development and expansion of abdominal aortic aneurysms (AAAs). 4,5 The histological features of AAA include atherosclerosis, loss of medial smooth muscle (with evidence of apoptosis), and loss of elastin (with remodeling of the connective tissue). Therefore, we wished to investigate the hypothesis that cadmium, from cigarettes, accumulates in the infrarenal abdominal aorta, thus stimulating aneurysmal dilatation. To test this hypothesis, we compared the concentration of cadmium in infrarenal aortas from patients with and without AAAs.After finding that the highest concentration of cadmium was in the medial layer of the aorta, we investigated whether similar concentrations of cadmium altered the metabol...
Studies have shown that alpha 1-adrenergic blockade reduces intimal hyperplasia in the rabbit aorta. In this study a selective alpha 1-adrenergic antagonist, doxazosin, has been used to examine whether this effect is persistent and dose dependent. Forty-eight New Zealand White rabbits underwent endothelial denudation of the abdominal aorta using a Fogarty balloon catheter. Test rabbits were given low-dose (2 mg) or high-dose (8 mg) doxazosin daily and all animals killed at either 1 or 12 weeks after the procedure. The aortas were harvested after fixation in situ with 4 per cent glutaraldehyde and neointimal hyperplasia was measured, using an x-y digitizer, as the percentage reduction in luminal cross-sectional area. At 1 week after surgery, rabbits receiving the low dose had a median area reduction of 7.7 per cent and those receiving the high dose a reduction of 8.2 per cent; both had significantly less intimal hyperplasia than control rabbits, which had a median area reduction of 14.8 per cent (P < 0.01). However, at 12 weeks, when compared with the 32.6 per cent reduction in the control group, only those rabbits receiving high-dose doxazosin had significantly less intimal hyperplasia, with a reduction of 5.5 per cent (P < 0.001). It is concluded that selective alpha 1-adrenergic blockade significantly reduces neointimal hyperplasia, that this effect is dose dependent, and that it persists for at least 3 months.
Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G>T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.
In rats, exposure to increased amounts of vitamin D during gestation and early life results in a reduction of aortic elastin content, number of elastic lamellae in the aorta and force generation in aortic rings.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.