The consequences of long and short‐term hypercholesterolemic diet consumption on the apoptotic cells and cathepsins expression in a new surgical model of abdominal aortic aneurysm in Wistar rats
Authors: Fernandes Cleverson Rodrigues , Mata Karina M , Shi Guo‐Ping , Sukhova Galina , Prado Cibele M , Floriano Elaine , Ramos Simone G 
Published: November 2023

Background

Abdominal aortic aneurysm (AAA) is a vascular disease which, despite the fact that it shares common risk factors with atherosclerosis, develops in parallel but as a partly independent process, through different pathogenic mechanisms. The AAA is frequently associated with atherosclerosis that increases the apoptosis, a crucial event in aneurysms formation and chronic inflammatory response. The objective of this study was investigate the apoptosis and the cathepsins mechanisms in AAA associated with the hypercholesterolemic diet consumption in a long and short‐term in a new surgical model of AAA induction in Wistar Rats.

Methodology

Forty eight male Wistar rats (150 g) were divided into eight groups. Four groups were euthanized on day 7 post AAA surgery induction and four groups on day 30 post‐surgery. Groups: Standard Diet control, 7 and 30 days groups (SDC7 and SDC30), High Fat Diet control (HFC7 and HFC30), Standard Diet Aneurysm (SDA7 and SDA30 days), High Fat Diet Aneurysm (HFA7 and HFA30 days). The animal protocols were approved by Committee on Animal Research of Ribeirão Preto Medical School of University of São Paulo and the animals were handled according to the guiding principles described in the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Results and Discussion

The aneurysms developed rapidly (7th days), similar as in human traumatic aneurysms. Macroscopic differences were observed in relation of structure and diameter between the control and AAA groups (dilatation up to 300%) on the histological level, the diet and post surgery time (7th and 30th days) didn't altered the AAA diameter. Visible hallmarks of AAA pathogenesis include inflammation, smooth muscle cell apoptosis, extracellular matrix degradation was observed in aneurysms from SDA and HFA groups on the 7th and 30th days. We observed an expressive increase of apoptotic and macrophages cells in the aneurysms groups, mainly in HFA group (P<0.05) on the 7th and 30th days. Similarly, collagenase and elastase activities (enzyme assay) were higher in Aneurysms groups. Cathepsins B/L/K/S activity (active site labeling) are higher in aneurysms groups as well (SDA and HFA; P<0.05).

Conclusion

These results suggest that aneurysms and hypercholesterolemic diet increased the expression of MMP‐9, MMP‐2, Cathepsins and apoptotic cells. Additionally the aneurysms developed from this new model have the same characteristics of the human traumatic AAA (such as mechanisms of formation, localization and time to development). The hypercholesterolemic diet have an important influence on apoptosis and cathepsins expression in a long and short‐term of diet consumption.

Support or Funding Information

FAPESP ‐Fundação de Amparo à Pesquisa do Estado de São PauloCNPq‐ Conselho Nacional de Desenvolvimento Científico e Tecnológico