Enhanced endoplasmic reticulum and mitochondrial stress in abdominal aortic aneurysm.

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, 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 to healthy donors. Higher gene expression of ATF6, IRE-1, XBP-1, CHOP, CRELD2 and 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 production and by a reduction in mitochondrial biogenesis in the vascular wall of AAA. The quantification of oxysterols, performed by liquid chromatography-(APCI)-mass spectrometry, showed that levels of 7-KC were significantly higher while those of 7α-hydroxycholesterol, 24-hydroxycholesterol and 27-hydroxycholesterol were lower in AAA patients compared to healthy donors. Interestingly, the levels of 7-KC correlate with the expression of ER stress markers.Our results...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research

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