Suppression of Experimental Abdominal Aortic Aneurysm in a Rat Model by the Phosphodiesterase 3 Inhibitor Cilostazol

Zhang, Qi; Huang, Jianhua; Xia, Renpeng; Duan, Xiaohui; Jiang, Yibo; Jiang, Qin; Sun, Weijia

doi:10.1016/j.jss.2011.01.017

Cited by 30 publications

(25 citation statements)

References 36 publications

(67 reference statements)

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“…Some studies explored the effect of cAMP agonist on the aneurysm. Cilostazol, a selective inhibitor of cAMP phosphodiesterase 3, could increase cellular cAMP and suppress the development of AAA in the mouse and rat models [41,42], which was consistent with the conclusion in this study.…”

Section: Discussionsupporting

confidence: 92%

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo

Qin

Tian

et al. 2019

Journal of Molecular and Cellular Cardiology

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Objective: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without an effective pharmaceutical treatment. Genetic studies have proved the involvement of smooth muscle phenotype switch in the development of AAA. The alpha subunit of the heterotrimeric G stimulatory protein (Gsα) mediates receptorstimulated production of cyclic adenosine monophosphate (cAMP). However, the role of smooth muscle Gsα in AAA formation remains unknown. Approach and results: In this study, mice with knockout of smooth muscle-specific Gsα (Gsα SMKO ) were generated by cross-breeding Gsα flox/flox mice with SM22-CreER T2 transgenic mice, induced in adult mice by tamoxifen treatment. Gsα deficiency induced a smooth muscle phenotype switch from a contractile to a synthetic state. Mechanically, Gsα deletion reduced cAMP level and increased the level of human antigen R (HuR), which binds with the adenylate uridylate-rich elements of the 3′ untranslated region of Krüppel-like factor 4 (KLF4) mRNA, thereby increasing the stability of KLF4. Moreover, genetic knockdown of HuR or KLF4 rescued the phenotype switch in Gsα-deficient smooth muscle cells. Furthermore, with acute infusion of angiotensin II, the incidence of AAA was markedly higher in ApoE −/− /Gsα SMKO than ApoE −/− /Gsα flox/flox mice and induced increased elastic lamina degradation and aortic expansion. Finally, the levels of Gsα and SM α-actin were significantly lower while those of HuR and KLF4 were higher in human AAA samples than adjacent nonaneurysmal aortic sections. Conclusions: Gsα may play a protective role in AAA formation by regulating the smooth muscle phenotype switch and could be a potential therapeutic target for AAA disease.is often accompanied by downregulation of multiple contractile proteins in aortic smooth muscle cells (SMCs) [4,5]. Furthermore, aortic intimal layer injury and inflammatory cell infiltration participate in the aneurysm progression via complicated mechanisms such as cytokine secretion and increased reactive oxygen species levels [3,6]. Finally, vascular collagen and elastin extracellular matrix is thought to undergo degradation by matrix metalloproteinases and contribute to AAA

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Section: Discussionsupporting

confidence: 92%

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo

Qin

Tian

et al. 2019

Journal of Molecular and Cellular Cardiology

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“…The native AAA model induced by elastase perfusion is a standard aneurysm model for experimental research in rodents [3], [22], [23], [24], [25], [26], [27], [28] and rabbits [29], [30], [31]. Anidjar et al [3] first introduced this method to create an AAA model in rats and suggested that elastase can lead to AAA development through enhanced inflammation response, elastolysis and subsequent destruction of the aortic walls.…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Rabbit Model of Abdominal Aortic Aneurysm via a Combination of Periaortic Calcium Chloride and Elastase Incubation

Zhong

et al. 2013

PLoS ONE

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BackgroundThe purpose of this study was to introduce a novel, simple and effective technique for creating a reliable rabbit model of abdominal aortic aneurysm (AAA) via a combination of periaortic calcium chloride (CaCl2) and elastase incubation.MethodsForty-eight New Zealand white rabbits were divided into four groups. The AAA model was developed via a 20-minute periaortic incubation of CaCl2 (0.5 mol/L) and elastase (1 Unit/µL) in a 1.5-cm aortic segment (Group CE). A single incubation of CaCl2 (Group C) or elastase (Group E) and a sham operation group (Sham Group) were used for the controls. Diameter was measured by serial digital subtraction angiography imaging on days 5, 15 and 30. Animals were sacrificed on day 5 and day 30 for histopathological and immunohistochemical studies.ResultsAll animals in Group CE developed aneurysm, with an average dilation ratio of 65.3%±8.9% on day 5, 86.5%±28.7% on day 15 and 203.6%±39.1% on day 30. No aneurysm was found in Group C, and only one aneurysm was seen on day 5 in Group E. Group CE exhibited less intima-media thickness, endothelial recovery, elastin and smooth muscle cell (SMC) content, but stronger expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and RAM11 compared to the controls.ConclusionsThe novel rabbit model of AAA created by using a combination of periaortic CaCl2 and elastase incubation is simple and effective to perform and is valuable for elucidating AAA mechanisms and therapeutic interventions in experimental studies.

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“…The native AAA model induced by elastase perfusion is a standard aneurysm model for experimental research in rodents [1, 3, 16–21] and rabbits [22, 23]. Although the pathogenesis of AAA is still unknown, it is generally believed that the effects of elastase stimulated an elastolytic and inflammatory response in the aortic walls [24] and resulted in the continual progress of aneurysm development.…”

Section: Discussionmentioning

confidence: 99%

Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits

Nie

Yan

et al. 2016

BioMed Research International

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Establishing an animal model of abdominal aortic aneurysm (AAA) is the key to study the pathogenesis and the pathophysiological features of AAAs. We investigated the effects of low-pressurized perfusion with different concentrations of elastase on aneurysm formation rate in the AAA model. Fifty male New Zealand white rabbits were randomly divided into A, B, C, D, and E groups. 10 μL of normal saline was perfused into the abdominal aorta in group A and 1 U/mL, 10 U/mL, 100 U/mL, or 200 U/mL of elastase was, respectively, perfused for the other four groups. All the animals were perfused for 7 min. Doppler ultrasound examinations of the abdominal aorta were performed before surgery and on day 14 after surgery. The rabbits were sacrificed and the perfused segment of the abdominal aorta was observed visually and after staining. The aneurysm formation rate of group A, group B, group C, group D, and group E was, respectively, 0%, 0%, 33.3%, 102.5–146.8%, and 241.5–255.2%. The survival rate of five groups was 90%, 90%, 90%, 90%, and 40%, respectively. So, we concluded that low-pressurized perfusion with 100 U/mL of elastase can effectively establish AAAs in rabbits with a high aneurysm formation rate.

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Suppression of Experimental Abdominal Aortic Aneurysm in a Rat Model by the Phosphodiesterase 3 Inhibitor Cilostazol

Cited by 30 publications

References 36 publications

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo

Smooth muscle-specific Gsα deletion exaggerates angiotensin II-induced abdominal aortic aneurysm formation in mice in vivo

Development of a Novel Rabbit Model of Abdominal Aortic Aneurysm via a Combination of Periaortic Calcium Chloride and Elastase Incubation

Effect of Low-Pressurized Perfusion with Different Concentration of Elastase on the Aneurysm Formation Rate in the Abdominal Aortic Aneurysm Model in Rabbits

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