Dataset Information

Interleukin-6 Receptor Signaling and Abdominal Aortic Aneurysm Growth Rates.

ABSTRACT:

Background

The Asp358Ala variant (rs2228145; A>C) in the IL (interleukin)-6 receptor ( IL6R) gene has been implicated in the development of abdominal aortic aneurysms (AAAs), but its effect on AAA growth over time is not known. We aimed to investigate the clinical association between the IL6R-Asp358Ala variant and AAA growth and to assess the effect of blocking the IL-6 signaling pathway in mouse models of aortic aneurysm rupture or dissection.

Methods

Using data from 2863 participants with AAA from 9 prospective cohorts, age- and sex-adjusted mixed-effects linear regression models were used to estimate the association between the IL6R-Asp358Ala variant and annual change in AAA diameter (mm/y). In a series of complementary randomized trials in mice, the effect of blocking the IL-6 signaling pathways was assessed on plasma biomarkers, systolic blood pressure, aneurysm diameter, and time to aortic rupture and death.

Results

After adjusting for age and sex, baseline aneurysm size was 0.55 mm (95% CI, 0.13-0.98 mm) smaller per copy of the minor allele [C] of the Asp358Ala variant. Change in AAA growth was -0.06 mm per year (-0.18 to 0.06) per copy of the minor allele; a result that was not statistically significant. Although all available worldwide data were used, the genetic analyses were not powered for an effect size as small as that observed. In 2 mouse models of AAA, selective blockage of the IL-6 trans-signaling pathway, but not combined blockage of both, the classical and trans-signaling pathways, was associated with improved survival ( P<0.05).

Conclusions

Our proof-of-principle data are compatible with the concept that IL-6 trans-signaling is relevant to AAA growth, encouraging larger-scale evaluation of this hypothesis.

SUBMITTER: Paige E

PROVIDER: S-EPMC6383754 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSeveral studies on the growth rates of abdominal aortic aneurysm (AAA) in Chinese population have been conducted; however, this issue remains unclear. The aim of this study is to systematically review published data of the AAA growth rates among people in China.MethodsWe conducted a comprehensive search of multiple databases to identify all studies of AAA growth in the Chinese population from inception until June 2017. AAA growth rates were combined to yield the growth rates at specified aneurysm diameter ranges, with using a random-effects model or fixed-effects model according to heterogeneity.ResultsA total of 8257 studies were initially identified and only 4 studies were eventually included. A random-effects analysis showed that the growth rates of AAA in Chinses population is ranging from 0.18 cm/year to 0.75 cm/year. The pooled mean growth rates among individuals with aneurysm measuring 3.0-3.9 cm, 4.0-5.9 cm and ≧ 6.0 cm in diameter were 0.21 cm/year (95% CI: 0.19 cm/year to 0.23 cm/year), 0.38 cm/year (95% CI: 0.33 cm/year to 0.43 cm/year), and 0.71 cm/year (95% CI: 0.64 cm/year to 0.77 cm/year) respectively. Further analysis found that the pooled mean growth rates for individuals with small AAA (diameters measuring 3.0-4.9 cm) was 0.28 cm/year (95% CI: - 0.06 cm/year to 0.61 cm/year)`and for individuals with large AAA (diameters ≥5.0 cm) was 0.75 cm/year (95% CI: 0.20 cm/year to 1.3 cm/year). Finally, meta-regression showed a strong trend of linear relationship between AAA growth rate and aneurysm diameter.ConclusionsThe growth rates of AAA in the Chinese population increase with AAA enlargement and appear to range from 0.18 cm/year in the smallest AAAs to 0.75 cm/year when the diameter exceeds 6 cm. However, based on current studies, it is difficult to estimate the accurate average AAA growth rate in Chinese patients. More large-scale, high-quality studies are required to achieve that. Overall, AAA growth rate increase with increased aneurysm diameter.