Effect of olmesartan and pravastatin on experimental cerebral aneurysms in rats

Kimura, Naoto; Shimizu, Hiroaki; Eldawoody, Hany; Nakayama, Tsuneyoshi; Saito, Atsushi; Tominaga, Teiji; Takahashi, Akira

doi:10.1016/j.brainres.2010.01.044

Cited by 38 publications

(29 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Damage to the endothelial layer is a universal pathological feature seen in both experimental and human IA (Draghia et al, 2008;Jamous et al, 2005b;Kataoka et al, 1999;Kimura et al, 2010;Nagata et al, 1981;Tada et al, 2010Tada et al, , 2011Tamura et al, 2009;Zhang et al, 2003). Morphological and pathological events leading to aneurysm formation in experimental models feature endothelial abnormalities as critical changes (Draghia et al, 2008;Jamous et al, 2005aJamous et al, ,b, 2007Kataoka et al, 1999;Kimura et al, 2010;Nagata et al, 1981;Tada et al, 2010Tada et al, , 2011Tamura et al, 2009).…”

Section: Changes In Constituents Of the Cerebral Blood Vessel Wall Inmentioning

confidence: 99%

“…Morphological and pathological events leading to aneurysm formation in experimental models feature endothelial abnormalities as critical changes (Draghia et al, 2008;Jamous et al, 2005aJamous et al, ,b, 2007Kataoka et al, 1999;Kimura et al, 2010;Nagata et al, 1981;Tada et al, 2010Tada et al, , 2011Tamura et al, 2009). Aneurysm formation and progression has been categorized into stages in experimental models with endothelial changes representing the earliest changes seen (including partial loss of endothelial cells and later intimal swelling).…”

Section: Changes In Constituents Of the Cerebral Blood Vessel Wall Inmentioning

confidence: 99%

“…Through their inhibitory action on NF-kB, three different statins were found to block various stages of the inflammatory reaction, decrease degenerative changes in the vessel wall and subsequently halt IA progression (Aoki et al, 2008b(Aoki et al, , 2009aKimura et al, 2010). However, despite these early promising results recent data question the efficacy of statins in reducing aneurysm development/progression.…”

Section: Therapies Targeting the Inflammatory Cascadementioning

confidence: 99%

“…Significant decrease in incidence of advanced IA (90% in control and 50% in treated group) ARB (Olmesartan) (Kimura et al, 2010) IA induced in rats with or without (n = 14) administration of low (3 mg/kg per day, n = 13) and high dose (10 mg/kg per day, n = 12) olmesartan…”

Section: Therapies Targeting the Inflammatory Cascadementioning

confidence: 99%

“…Promising results were reported with an inhibitor of phosphodiesterase-4 (Ibudilast), a cyclic adenosine monophosphate-specific enzyme involved in various inflammatory diseases . Several angiotensin receptor blockers were also tested with varying results (Aoki et al, 2009d;Kimura et al, 2010;Tamura et al, 2009). Perhaps, the most impressive strategy, thus far, involves NF-kB inhibition that caused a dramatic decrease in the inflammatory response and IA incidence in rats (a 60% decrease; Aoki et al, 2007c).…”

Section: Intracranial Aneurysms and Inflammationmentioning

confidence: 99%

See 4 more Smart Citations

Biology of Intracranial Aneurysms: Role of Inflammation

Chalouhi

Ali

Jabbour

et al. 2012

J Cereb Blood Flow Metab

440

418

View full text Add to dashboard Cite

Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA.

show abstract

Section: Changes In Constituents Of the Cerebral Blood Vessel Wall Inmentioning

confidence: 99%

Section: Changes In Constituents Of the Cerebral Blood Vessel Wall Inmentioning

confidence: 99%

Section: Therapies Targeting the Inflammatory Cascadementioning

confidence: 99%

Section: Therapies Targeting the Inflammatory Cascadementioning

confidence: 99%

Section: Intracranial Aneurysms and Inflammationmentioning

confidence: 99%

See 3 more Smart Citations

Biology of Intracranial Aneurysms: Role of Inflammation

Chalouhi

Ali

Jabbour

et al. 2012

J Cereb Blood Flow Metab

440

418

View full text Add to dashboard Cite

show abstract

Molecular Basis for Intracranial Aneurysm Formation

Fukuda

Aoki

2014

Acta Neurochirurgica Supplement

View full text Add to dashboard Cite

Intracranial aneurysm (IA) is a socially important disease both because it has a high prevalence and because of the severity of resultant subarachnoid hemorrhages after IA rupture. The major concern of current IA treatment is the lack medical therapies that are less invasive than surgical procedures for many patients. The current situation is mostly caused by a lack of knowledge regarding the regulating mechanisms of IA formation. Hemodynamic stress, especially high wall shear stress, loaded on arterial bifurcation sites is recognized as a trigger of IA formation from studies performed in the field of fluid dynamics. On the other hand, many studies using human specimens have also revealed the presence of active inflammatory responses, such as the infiltration of macrophages, in the pathogenesis of IA. Because of these findings, recent experimental studies, mainly using animal models of IA, have revealed some of the molecular mechanisms linking hemodynamic stress and long-lasting inflammation in IA walls. Currently, we propose that IA is a chronic inflammatory disease regulated by a positive feedback loop consisting of the cyclooxygenase (COX)-2 - prostaglandin (PG) E2 - prostaglandin E receptor 2 (EP2) - nuclear factor (NF)-κB signaling pathway triggered under hemodynamic stress and macrophage infiltration via NF-κB-mediated monocyte chemoattractant protein (MCP)-1 induction. These findings indicate future directions for the development of therapeutic drugs for IAs.

show abstract