Impaired Acetylcholine-Induced Endothelium-Dependent Aortic Relaxation by Caveolin-1 in Angiotensin II-Infused Apolipoprotein-E (ApoE−/−) Knockout Mice

Seto, Sai Wang; Krishna, Smriti Murali; Yu, Hongyou; Liu, David; Khosla, Surabhi; Golledge, Jonathan

doi:10.1371/journal.pone.0058481

Cited by 33 publications

(34 citation statements)

References 36 publications

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“…Consistent with our previous report (Pojoga et al, 2008), ACh-induced aortic relaxation was greater in cav-1 2/2 mice than in WT mice, supporting an increase in endothelium-derived relaxing factor(s) in cav-1 deficiency states. This is also supported by the report that pharmacological disruption of caveolae and cav-1 using methyl-b-cyclodextrin in isolated aorta from AngII-infused apolipoprotein E knockout mice caused enhancement of the ACh-induced concentrationrelaxation curve when compared with vehicle control (Seto et al, 2013). Also, the present Western blots revealed an increase in cardiac eNOS protein in cav-1 2/2 versus WT mice.…”

Section: Discussionsupporting

confidence: 89%

Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide–High Angiotensin II–Induced Cardiovascular Injury

Pojoga

Yao

Opsasnick

et al. 2015

J Pharmacol Exp Ther

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Aldosterone interacts with mineralocorticoid receptor (MR) to stimulate sodium reabsorption in renal tubules and may also affect the vasculature. Caveolin-1 (cav-1), an anchoring protein in plasmalemmal caveolae, binds steroid receptors and also endothelial nitric oxide synthase, thus limiting its translocation and activation. To test for potential MR/cav-1 interaction in the vasculature, we investigated if MR blockade in cav-1-replete or -deficient states would alter vascular function in a mouse model of low nitric oxide (NO)-high angiotensin II (AngII)-induced cardiovascular injury. Wild-type (WT) and cav-1 knockout mice (cav-1 2 /2 ) consuming a high salt diet (4% NaCl) received N v -nitro-L-arginine methyl ester (L-NAME) (0.1-0.2 mg/ml in drinking water at days 1-11) plus AngII (0.7-2.8 mg/kg per day via an osmotic minipump at days 8-11) 6 MR antagonist eplerenone (EPL) 100 mg/kg per day in food. In both genotypes, blood pressure increased with L-NAME 1 AngII. EPL minimally changed blood pressure, although its dose was sufficient to block MR and reverse cardiac expression of the injury markers cluster of differentiation 68 and plasminogen activator inhibitor-1 in L-NAME1AngII treated mice. In aortic rings, phenylephrine and KCl contraction was enhanced with EPL in L-NAME1AngII treated WT mice, but not cav-1 2/2 mice.AngII-induced contraction was not different, and angiotensin type 1 receptor expression was reduced in L-NAME 1 AngII treated WT and cav-1 2/2 mice. In WT mice, acetylcholine-induced relaxation was enhanced with L-NAME 1 AngII treatment and reversed with EPL. Acetylcholine relaxation in cav-1 2/2 mice was greater than in WT mice, not modified by L-NAME 1 AngII or EPL, and blocked by ex vivo L-NAME, 1H-(1,2,4)oxadiazolo(4,3-a) quinoxalin-1-one (ODQ), or endothelium removal, suggesting the role of NO-cGMP. Cardiac endothelial NO synthase was increased in cav-1 2/2 versus WT mice, further increased with L-NAME 1 AngII, and not affected by EPL. Vascular relaxation to the NO donor sodium nitroprusside was increased with L-NAME 1 AngII in WT mice but not in cav-1 2/2 mice. Plasma aldosterone levels increased and cardiac MR expression decreased in L-NAME 1 AngII treated WT and cav-1 2/2 mice and did not change with EPL. Thus, during L-NAME 1 AngII induced hypertension, MR blockade increases contraction and alters vascular relaxation via NO-cGMP, and these changes are absent in cav-1 deficiency states. The data suggest a cooperative role of MR and cav-1 in regulating vascular contraction and NO-cGMP-mediated relaxation during low NO-high AngII-dependent cardiovascular injury.

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Section: Discussionsupporting

confidence: 89%

Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide–High Angiotensin II–Induced Cardiovascular Injury

Pojoga

Yao

Opsasnick

et al. 2015

J Pharmacol Exp Ther

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“…Blood pressure and heart rate were measured repeatedly and the measurements were averaged from ten consecutive measurements. Good reproducibility of this technique has been previously established [39,41,42].…”

Section: Non-invasive Tail-cuff Blood Pressure Measurementsmentioning

confidence: 83%

“…The aortas were excised and placed on a graduated template and digitally photographed (Coolpix 4500, Nikon). The maximum ex vivo external aortic diameters of the aortic arch, thoracic aorta (TA), the suprarenal abdominal aorta (suprarenal aorta (SRA)) and the infrarenal aorta (IRA) were measured as previously reported [38,41,42] using Adobe Photoshop software (CS6). Representative portions of aortic segments were dissected and stored in either optimal cutting compound (OCT, ProSciTech) compound or RNA later (Qiagen) for subsequent experiments.…”

Section: Measurement Of Aortic Diameters In Micementioning

confidence: 99%

“…All animals were acclimatized to the device 2 days before measuring the blood pressure as previously established [42]. All mice were allowed to acclimatize to the restrainer chamber on a warm pad for 10 min in a temperature-controlled room before the measurements and multiple measurements were recorded at each time point, i.e.…”

Section: Non-invasive Tail-cuff Blood Pressure Measurementsmentioning

confidence: 99%

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High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice

et al. 2017

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Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman's rho − 0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40; 95% confidence interval (CI): 0.19-0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1 −/− ApoE −/− , n=20) and control mice (ApoE −/− , n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1 −/− ApoE −/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1 −/− ApoE −/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1 −/− ApoE −/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1 −/− ApoE −/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.

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“…Also, mitochondria may endogenously produce Ang II [36][37][38]. Several animal studies show that Ang II causes and contributes to aortic endothelial dysfunction [39][40][41]. It promotes abnormal vasomotion, a procoagulant state and transmigration of inflammatory cells into the vessel wall [42].…”

Section: Role Of Ras In Atherosclerosis Developmentmentioning

confidence: 99%

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Kolaković¹,

Živković²,

Stanković³

2017

Renin-Angiotensin System - Past, Present and Future

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The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

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Impaired Acetylcholine-Induced Endothelium-Dependent Aortic Relaxation by Caveolin-1 in Angiotensin II-Infused Apolipoprotein-E (ApoE−/−) Knockout Mice

Cited by 33 publications

References 36 publications

Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide–High Angiotensin II–Induced Cardiovascular Injury

Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide–High Angiotensin II–Induced Cardiovascular Injury

High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice

Involvement of the Renin‐Angiotensin System in Atherosclerosis

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