Endothelial and Smooth Muscle Cells from Abdominal Aortic Aneurysm Have Increased Oxidative Stress and Telomere Attrition

Background: Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls. Methods: TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG). Results and Conclusions: Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed. © 2012 Cafueri et al

Telomere shortening and increased oxidative stress are restricted to venous tissue in patients with varicose veins: A merely local disease?

Shortened telomere length (TL) and oxidative stress have been described in several vascular disorders at both the tissue and circulating level. However, to our knowledge, there are no reports about TL associated with varicose vein (VV) disease. This paper aimed to evaluate, at the tissue and circulating level, TL and oxidative stress in VV disease, compared to the corresponding counterparts from abdominal aortic aneurysm (AAA) patients and control healthy subjects. TL was measured using quantitative fluorescence in situ hybridization (Q-FISH). Oxidative stress was evaluated by measuring the malondialdehyde (MDA) concentration by thiobarbituric acid reactive substance/s (TBARS) assay. At the vascular tissue level, VV patients had shortened TL and a high MDA concentration, similarly to AAA patients. Conversely, blood lymphocytes and epidermal cells from VV patients had a TL similar to healthy controls and significantly longer than the same cells from AAA patients. Moreover, the MDA concentration in plasma from VV patients was significantly lower than from the AAA group. Linear regression analysis showed a statistically significant inverse correlation between the blood lymphocyte TL and plasma MDA level. Our results suggest that, unlike AAA, telomere attrition in VV tissue is not a systemic phenomenon but it may be attributable to tissue microenvironment conditions and possibly to high local oxidative stress

A retrospective study on short term results with straight graft vs. bifurcated graft in abdominal aortic aneurysms: a single center experience.

Aim: The aim of this paper was to compare in a retrospective study the outcome of aortoaortic graft (straight graft) versus aortoiliac graft (bifurcated graft) with regards to periprocedural and 30-day after surgery complications. Methods: From January 2004 to December 2009 377 patients underwent elective open surgery for infrarenal abdominal aortic aneurysm. Data were collected in a dedicated database. Group A includes patients treated with straight graft (N.=186) whereas group B, patients treated with bifurcated graft (N.=191). Outcome data include duration of surgical procedure, blood loss, peri- and postprocedural complications, hospital stay, 30-day mortality and complications. Following some authors, we set our cut-off for choosing a bifurcated graft when one or both Iliac Arteries were wider than 18 mm in diameter and the patient had a reasonable life expectancy. Results: duration of surgical procedure was 183 minutes in the group A vs. 216 minutes in the group B (P<0.01). Blood loss was 554 mL and 720 mL, in the groups A and B respectively (P<0.01). The difference between other results evaluated was not statistically significant. Conclusion: In statistics terms, this retrospective study showed no relevant differences between straight graft and bifurcated graft with regard to mortality and major complications during the peri- and postoperatory period. Hence, as a conclusion, we could assert that if the iliac artery diameter is 18 mm a bifurcated graft could be used, without any increase in morbidity and mortality rates

Carotid endarterectomy by eversion technique: primary singlecenter technique

Beneficial effect of carotid endarterectomy in symptomatic and asymptomatic patients with extra cranial atherosclerotic carotid stenosis has been demonstrated in severat targe randomized studies, measuring preservation of neurologic function with a low incidence of restenosis. Eversion carotid endarterectomy (E-CEA), using a transection of the internal carotid artery at the bulb with eversion endarterectomy, a direct visualization of the endpoint and a direct anastomosis to the common carotid artery has been proposed as an acceptable alternative to lower the risk of restenosis, retaining the advantages of the standard longitudinal technique, either with simple or patch closure. The aim of this study was to evaluate the results of E-CEA carried out in our Center over the past five years

Tecniche di Endarterectomia carotidea per eversione a confronto: Studio prospettico randomizzato di un singolo centro. risultati preliminari.

Uno studio prospettico randomizzato che mette a confronto due tecniche di endoarterectomia carotidea per eversione, la tecnice secondo De Bakey e la tecnica secondo Etheredge. Lo studio prevede l'arruolamento, l'intervento e il follow-up du 276 pazienti, per osservare e confrontare il tasso di restenosi e complicanze nei due gruppi. I risultati preliminari mostrano una significativa riduziopne del tasso di restenosi nel gruppo di pazienti operati con la tecnica Etheredge

Telomere length and oxidative DNA damage in lymphocytes from each individual AAA patient and control.

<p><b>A</b>) Telomere length of peripheral blood lymphocytes from 23 patients with abdominal aortic aneurysms (AAA), and 34 healthy donors. Bars represent the mean. <b>B</b>) Lymphocytes interphase nuclei from an AAA patient hybridized with Cy3-PNA telomeric probe (red signals). <b>C</b>) Oxidative DNA damage in peripheral blood lymphocytes from 19 patients with AAA, and 23 healthy donors. <b>D</b>) A representative immunostaining of anti-8-oxo-dG (green) of blood lymphocytes from an AAA patient. Arrows show nuclei intensively staining for 8-oxo-dG (green). <b>D</b>) Immunostaining of anti-8-oxo-dG (green) of blood lymphocytes from an healthy donor. Arrow shows nucleus with several small positive regions.</p

γH2AX staining patterns observed in EC and VSMC from patients with AAA.

<p><b>A</b>) Aortic aneurysmatic wall derived EC stained with anti-CD31 (green) and anti-γH2AX (red) mAbs. <b>B</b>) Aortic aneurysmatic wall derived VSMC stained with anti-α-smooth muscle actin (green) and anti-γH2AX (red) mAbs. Focal staining for γH2AX is evident (A, B). Nuclei stained with DAPI (A, B). Magnification, 100× (A, B). <b>C</b>) γH2AX-positive foci were significantly more abundant in EC and VSMC from AAA wall compared to controls (p = 0.006 and p = 0.010 respectively).</p

Telomere length of EC, VSMC, blood lymphocytes and epidermal cells from patients with AAA and controls.

<p><b>A</b>) Telomeres length in EC from 21 AAA patients and in EC from 20 normal aorta. <b>B</b>) Telomeres length in VSMC from 21 AAA patients and in VSMC from 20 normal aorta. <b>C</b>) Telomeres length in epidermal cells from patients with 11 AAA and in these same cells from 6 controls. <b>D</b>) Telomeres length in peripheral blood lymphocytes in 23 AAA patients and in 34 controls.</p

Median telomere fluorescence.

<p>A minimum of 20 nuclei were scanned for every sample and the mean value of the fluorescence ratios of all cells analyzed was calculated.</p