Lower  levels  of  Caveolin-1  and  higher  levels  of  endothelial  nitric   oxide  synthase  are  observed  in  abdominal  aortic  aneurysm   patients  treated  with  simvastatin

Kowalska, Karolina; Habrowska-Górczyńska, Dominika Ewa; Neumayer, Christoph; Bolliger, Michael; Domenig, Christoph; Piastowska-Ciesielska, Agnieszka Wanda; Huk, Ihor; Piechota-Polańczyk, Aleksandra

doi:10.18388/abp.2017_2305

Cited by 17 publications

(8 citation statements)

References 39 publications

(43 reference statements)

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“… 10 Furthermore, simvastatin treatment decreased Cav1 expression and increased eNOS (endothelial nitric oxide synthase) expression in patients who underwent abdominal aortic aneurysm repair. 11 The study highlighted a potential link between statins and Cav1 and additionally suggested a possible pleiotropic benefit of statins outside of lipid reduction. Statins may exert their effects on eNOS through Cav1 as endocytosis of caveolae has been shown to mediate the activation of eNOS.…”

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confidence: 92%

Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

et al. 2020

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Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin’s aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1–43.2) lower aldosterone level ( P =0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels ( P =0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant ( P =0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin’s aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.

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confidence: 92%

Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone

et al. 2020

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“…In addition to their lipid-lowering capacity, statin can improve endothelial function via increasing endothelial nitric oxide synthase expression and BH4 bioavailability (Kosmidou et al, 2007;Wenzel et al, 2008). In contrast, statin treatment can also diminish IL-6 and MCP1 levels in AAA models (Kowalska et al, 2018). In this study, we focused on the protective effects of endothelium-specific BRG1 deletion in AAA, and our results demonstrated that BRG1 deletion in endothelial cells significantly inhibited Ang II-induced AAA development.…”

Section: Discussionmentioning

confidence: 87%

Brahma-Related Gene 1 Deficiency in Endothelial Cells Ameliorates Vascular Inflammatory Responses in Mice

Zhang

Wang

Song

et al. 2020

Front. Cell Dev. Biol.

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Endothelial dysfunction plays an important role in promoting the progression of disease genesis such as atherosclerosis and abdominal aortic aneurysm (AAA). The physiological unbalance of endothelial cells is a major pathological basis. In this present study, we investigated Brahma-related gene 1 (BRG1), a chromatin remodeling protein, was in mouse models of diabetic atherosclerosis and AAA, focusing on its role in endothelial dysfunction. We report that compared with their wild-type (WT, ApoE–/–; BRG1fl/fl) littermates, endothelium conditional BRG1 knockout mice (CKO, ApoE–/–; BRG1fl/fl; CDH5-cre) exhibited an alleviated phenotype of diabetic atherosclerosis. Immunohistochemically staining and real-time PCR analysis demonstrated fewer macrophages recruitment with a reduction of vascular inflammatory in CKO mice compared with WT mice. Further research in the Ang-II induced AAA model revealed that BRG1 deficiency had the protective effects on endothelium conditional BRG1 deletion, evidenced by the downregulation of pro-inflammatory mediators [interleukin (IL)-1β and IL-6, not tumor necrosis factor-α (TNF-α)] in the vessels of CKO mice compared with WT mice. In Ea.hy926 cell lines, anti-BRG1 small interfering RNA and PFI-3 treatment obviously alleviated tumor necrosis factor-α-induced IL-6 and CCL2 expression, and further research demonstrated that the BRG1 inhibition in endothelial cells not only decreased c-Fos expression but also blocked the c-Fos translocation into nuclei. In conclusion, our results suggest that endothelial BRG1 deficiency may protect the mice from diabetic atherosclerosis and AAA via inhibiting inflammatory response in vessels.

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“…The core function of the endothelium is to provide an anti-adhesive, antithrombotic surface. Cytokines and hypercholesterolaemia stimulate endothelial dysfunction and result in impaired production of endothelial nitric oxide synthase (eNOS) (30)(31)(32). NO mediates several benefits, including vascular relaxation and suppression of smooth-muscle-cell proliferation, leukocyte, or platelet-endothelial interactions and exocytosis (33).…”

Section: Anti-inflammatory Actions Of Statinsmentioning

confidence: 99%