Abdominal aortic aneurysm (AAA) is a degenerative vascular disease with a complex aetiology that remains to be fully elucidated. Clinical management of AAA is limited to surgical repair, while an effective pharmacotherapy is still awaited. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction have been involved in the pathogenesis of cardiovascular diseases (CVDs), although their contribution to AAA development is uncertain. Therefore, we aimed to determine their implication in AAA and investigated the profile of oxysterols in plasma, specifically 7-ketocholesterol (7-KC), as an ER stress inducer. In the present study, we determined aortic ER stress activation in a large cohort of AAA patients compared with healthy donors. Higher gene expression of activating transcription factor (ATF) 6 (ATF6), IRE-1, X-binding protein 1 (XBP-1), C/EBP-homologous protein (CHOP), CRELD2 and suppressor/enhancer of Lin-12-like (SEL1L) and greater protein levels of active ATF6, active XBP1 and of the pro-apoptotic protein CHOP were detected in human aneurysmatic samples. This was accompanied by an exacerbated apoptosis, higher reactive oxygen species (ROS) production and by a reduction in mitochondrial biogenesis in the vascular wall of AAA. The quantification of oxysterols, performed by liquid chromatography-(atmospheric pressure chemical ionization (APCI))-mass spectrometry, showed that levels of 7-KC were significantly higher while those of 7α-hydroxycholesterol (HC), 24-HC and 27-HC were lower in AAA patients compared with healthy donors. Interestingly, the levels of 7-KC correlate with the expression of ER stress markers. Our results evidence an induction of ER stress in the vascular wall of AAA patients associated with an increase in circulating 7-KC levels and a reduction in mitochondrial biogenesis suggesting their implication in the pathophysiology of this disease.
Abdominal aortic aneurysm (AAA) is increasing due to aging of the population and is a major cause of death among the elderly. Ultrasound screening programs are useful in early diagnosis, but aneurysm size is not always a good predictor of rupture. Our aim was to analyze the value of circulating molecules related to oxidative stress and inflammation as new biomarkers to assist the management of AAA. The markers were quantified by ELISA, and their expression in the aneurysmal wall was studied by real-time PCR and by immunostaining. Correlation analysis of the studied markers with aneurysm diameter and peak wall stress (PWS), obtained by finite element analysis, and multivariate regression analysis to assess potential confounding factors were performed. Our study shows an extensive inflammatory infiltration in the aneurysmal wall, mainly composed by T-cells, macrophages and B-cells and altered levels of reactive oxygen species (ROS), IgM, IgG, CD38, GDF15, S100A4 and CD36 in plasma and in the aneurysmal tissue of AAA patients compared with controls. Circulating levels of IgG, CD38 and GDF15 positively correlated with abdominal aortic diameter, and CD38 was correlated with PWS. Our data show that altered levels of IgG, CD38 and GDF15 have potential diagnostic value in the assessment of AAA.
The MDRD-4 GFR was a better predictor of risk of death or infarction than classical cardiovascular risk factors in patients with PAD. This suggests that its routine use in the initial evaluation in patients with PAD is beneficial.
Objective: To determine the prevalence and risk factors associated with peripheral arterial disease (PAD) in Northern Barcelona at 65 years of age. Methods: A single-center, cross-sectional study, including males and females 65 years of age, health care cardholders of Barcelona Nord. PAD was defined as an ankle–brachial index (ABI) < 0.9. Attending subjects were evaluated for a history of common cardiovascular risk factors. A REGICOR score was obtained, as well as a physical examination and anthropometric measurements. Results: From November 2017 to December 2018, 1174 subjects were included: 479 (40.8%) female and 695 (59.2%) male. Overall prevalence of PAD was 6.2% (95% CI: 4.8–7.6%), being 7.9% (95% CI: 5.9–9.9%) in males and 3.8% (95% CI: 2.1–5.5%) in females. An independent strong association was seen in male smokers and diabetes, with ORs pf 7.2 (95% CI: 2.8–18.6) and 1.8 (95% CI: 1.0–3.3), respectively, and in female smokers and hypertension, with ORs of 5.2 (95% CI: 1.6–17.3) and 3.3 (95% CI: 1.2–9.0). Male subjects presented with higher REGICOR scores (p < 0.001). Conclusion: Higher-risk groups are seen in male subjects with a history of smoking and diabetes and female smokers and arterial hypertension, becoming important subgroups for our primary healthcare centers and should be considered for ABI screening programs.
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