Early Results after Exclusion of Popliteal Aneurysms with an Endoprosthesis.

Objectives: To evaluate safety and efficacy of endoprosthesis implantation for the exclusion of popliteal artery aneurysm (PAA). Methods: Elective asymptomatic patients with aneurysm > 20 mm and symptomatic patients with endovascular therapy of PAA were included. The proportion of patients with critical limb ischemia (presence of rest pain or tissue loss) was high at 32.1%, 21.6% of the patients had acute ischemia with symptoms persisting shorter than 14 days. The primary study endpoint was the target lesion revascularization (TLR) rate at 12 months. Secondary endpoints included technical success, periinterventional adverse events, primary patency at 6, 12 and 24 months, TLR rate at 24 months, predictors on reintervention, change in in clinical symptoms using the Rutherford-Becker classification (RBC), amputation and mortality rate. One hundred thirty-four patients (68.3±10.6 years, 88.8% male) were treated with a Viabahn® endoprosthesis (W.L. Gore & Associates Inc., Flagstaff, AZ, USA). Results: The average aneurysm diameter was 2.5±0.87 cm. In 41%, occlusion of the aneurysm was present. TLR rate was 31.3% and 38.8% after 12 and 24 months, respectively. Primary patency rates were 69.1%, 52.3% and 42.6% at 6, 12 and 24 months, respectively. Univariate logistic regression analysis revealed age as a predictor of reintervention and in the multivariable analysis it was treatment with lysis. An improvement in RBC was seen at all-time points. Two major amputations (1.5%) were performed and the mortality rate at 24 months was 5.2%. Conclusion: Primary patency rate after endovascular exclusion of PAA is low. However, limb salvage rate is high.

Contribution of the α8 integrin chain to the expression of extracellular matrix components.

In the kidney, the α8 integrin chain (itga8) is expressed in mesenchymal cells and is upregulated in fibrotic disease. We hypothesized that itga8 mediates a profibrotic phenotype of renal cells by promoting extracellular matrix and cytokine expression. Genetic itga8 deficiency caused complex changes in matrix expression patterns in mesangial and smooth-muscle cells, with the only concordant effect in both cell types being a reduction of collagen III expression. Silencing of itga8 with siRNA led to a decline of matrix turnover with repression of matrix metalloproteinases and reduction of matrix production. In contrast, de novo expression of itga8 in tubular epithelial cells resulted in reduced collagen synthesis. Overexpression of itga8 in fibroblasts did not change the expression of matrix molecules or regulators of matrix turnover. Thus, the influence of itga8 on the expression of matrix components was not uniform and celltype dependent. Itga8 seems unlikely to exert overall profibrotic effects in renal cells.

Lack of α8 integrin leads to morphological changes in renal mesangial cells, but not in vascular smooth muscle cells.

BACKGROUND: Extracellular matrix receptors of the integrin family are known to regulate cell adhesion, shape and functions. The α8 integrin chain is expressed in glomerular mesangial cells and in vascular smooth muscle cells. Mice deficient for α8 integrin have structural alterations in glomeruli but not in renal arteries. For this reason we hypothesized that mesangial cells and vascular smooth muscle cells differ in their respective capacity to compensate for the lack of α8 integrin. RESULTS: Wild type and α8 integrin-deficient mesangial cells varied markedly in cell morphology and expression or localization of cytoskeletal molecules. In α8 integrin-deficient mesangial cells α-smooth muscle actin and CTGF were downregulated. In contrast, there were no comparable differences between α8 integrin-deficient and wild type vascular smooth muscle cells. Expression patterns of integrins were altered in α8 integrin-deficient mesangial cells compared to wild type mesangial cells, displaying a prominent overexpression of α2 and α6 integrins, while expression patterns of the these integrins were not different between wild type and α8 integrin-deficient vascular smooth muscle cells, respectively. Cell proliferation was augmented in α8 integrin-deficient mesangial cells, but not in vascular smooth muscle cells, compared to wild type cells. CONCLUSIONS: Our findings suggest that α8 integrin deficiency has differential effects in mesangial cells and vascular smooth muscle cells. While the phenotype of vascular smooth muscle cells lacking α8 integrin is not altered, mesangial cells lacking α8 integrin differ considerably from wild type mesangial cells which might be a consequence of compensatory changes in the expression patterns of other integrins. This could result in glomerular changes in α8 integrin-deficient mice, while the vasculature is not affected in these mice.