Vascular Calcification in Rodent Models—Keeping Track with an Extented Method Assortment

Herrmann, Jaqueline; Gummi, Manasa Reddy; Xia, Mengdi; Giet, Markus van der; Tölle, Markus; Schuchardt, Mirjam

doi:10.3390/biology10060459

Cited by 11 publications

(22 citation statements)

References 145 publications

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“…We firstly determined the ameliorative effect of berberine on VC in high-dose vitamin D 3 -induced aortic calcification and beta-glycerophosphate-induced VSMC calcification in rats, which are the 2 general VC models widely used in vivo and in vitro , respectively. 29 Histology is a well-established standard lab technology and therefore, to date, is considered the gold standard. Staining with Alizarin red is a well-established method to detect calcium.…”

Section: Discussionmentioning

confidence: 99%

“…The calcified aorta model in VSMCs of rats was induced according to the previously described method with minor modifications. 29 Briefly, after the male Sprague-Dawley rats (150–160 g) were sacrificed by cervical vertebra luxation, the thoracic aortas were exercised, external connective tissue was removed, and then cut into small pieces. The pieces were placed in Dulbecco's modified eagle medium with 4 g/L glucose, 10 mmol/L sodium pyruvate and 20% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

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The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress

Li¹,

Zheng²,

Cao

et al. 2022

Journal of Cardiovascular Pharmacology

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Vascular calcification (VC), which currently cannot be prevented or treated, is an independent risk factor for cardiovascular events. We aimed to investigate the ameliorative effect of berberine on VC via the activation of Akt signaling and inhibition of endoplasmic reticulum stress (ERS). The VC model was induced by high-dose Vitamin D 3 in rats and beta-glycerophosphate in primary vascular smooth muscle cells of rat aortas, which were evaluated by Alizarin red staining to determine the calcium content and alkaline phosphatase activity. ERS was determined by the levels of GRP78 and CHOP, whereas that of the Akt signaling pathway was determined by the levels of phosphorylated Akt and GSK3b. VC was significantly ameliorated by berberine treatment in vivo and in vitro, and the inhibition of ERS and the activation of the Akt/ GSK3 signaling pathway. In the vascular smooth muscle cells of primary rats, tunicamycin, an ERS activator, blocked the ameliorative effect of berberine on VC and ERS, but not the activation of Akt/GSK3. The ameliorative effects of berberine on VC, ERS, and the Akt signaling pathway were all prevented by inhibitor IV. Fourphenylbutyric acid, an ERS inhibitor, can restore the ameliorative effect of berberine on VC and ERS that was blocked by inhibitor IV. Our results are the first to demonstrate the ameliorative effect of VC that was mediated by the activation of the Akt signaling pathway and inhibition of ERS. These results may provide a new pharmaceutical candidate for the prevention and treatment of VC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress

Li¹,

Zheng²,

Cao

et al. 2022

Journal of Cardiovascular Pharmacology

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“…This genetic KO model develops AVS as early as 3 weeks in females and 6 weeks in males, maintaining increased AV peak velocities and pressures throughout their lifetime. Our mouse model of spontaneous AVS presents as a new avenue for AVS research, with a shorter development time compared to other AVS mouse models which normally take > 20 weeks to develop hemodynamically stable AVS ( 25 , 26 ). Also, our AVS model does not need to feed the animals a special diet or induce a mechanical injury ( 25 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Role of endothelial CXCR4 in the development of aortic valve stenosis

Winnicki

Gadd²,

Ohanyan³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundCXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS.Materials and methodsWe generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4fl/fl mice with Tie2-Cre mice to study the role of endothelial cell CXCR4 in AVS. CXCR4fl/fl mice were used as controls. Echocardiography was used to assess the aortic valve and cardiac function. Heart samples containing the aortic valve were stained using Alizarin Red for detection of calcification. Masson’s trichrome staining was used for the detection of fibrosis. The apex of the heart samples was stained with wheat germ agglutinin (WGA) to visualize ventricular hypertrophy.ResultsCompared with the control group, the deletion of CXCR4 in endothelial cells led to significantly increased aortic valve peak velocity and aortic valve peak pressure gradient, with decreased aortic valve area and ejection fraction. EC CXCR4 KO mice also developed cardiac hypertrophy as evidenced by increased diastolic and systolic left ventricle posterior wall thickness (LVPW), cardiac myocyte size, and heart weight (HW) to body weight (BW) ratio. Our data also confirmed increased microcalcifications, interstitial fibrosis, and thickened valvular leaflets of the EC CXCR4 KO mice.ConclusionThe data collected throughout this study suggest the deletion of CXCR4 in endothelial cells is linked to the development of aortic valve stenosis and left ventricular hypertrophy. The statistically significant parameters measured indicate that endothelial cell CXCR4 plays an important role in aortic valve development and function. We have compiled compelling evidence that EC CXCR4 KO mice can be used as a novel model for AVS.

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“…Chronic kidney(CKD) disease with vascular calcification is a strong predictor of cardiovascular disease ( 1 , 2 ). Understanding the possible etiology and mechanism of vascular calcification is of great significance for reducing the incidence and mortality of cardiovascular and cerebrovascular events in patients with CKD ( 3 , 4 ) As known, aldosterone (Aldo) is known to be a participant in the metabolites of the renin-angiotensin- Aldo system, which not only regulates blood volume and consequently blood pressure homeostasis by regulating sodium retention, but also stimulates the process of vascular calcification ( 5 , 6 ). Evidence has shown the plasma Aldo level in patients with CKD is significantly increased, and with the increase of plasma Aldo level, the occurrence of vascular calcification is on the rise ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of AIF-1 in the Aldosterone-Induced Vascular Calcification Related to Chronic Kidney Disease: Evidence From Mice Model and Cell Co-Culture Model

et al. 2022

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Increasing evidence suggests that aldosterone (Aldo) plays an essential role in vascular calcification which is a serious threat to cardiovascular disease (CVD) developed from chronic kidney disease (CKD). However, the exact pathogenesis of vascular calcification is still unclear. First, we established CKD-associated vascular calcification mice model and knockout mice model to investigate the causal relationship between allograft inflammatory factor 1 (AIF-1) and vascular calcification. Then, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) co-culture experiments were performed to further explore the mechanisms of calcification. The results of the Aldo intervention mice model and transgenic mice model showed that Aldo could cause calcification by increasing the AIF-1 level. The results of in vitro co-culture model of ECs and VSMCs showed that AIF-1 silence in ECs may alleviate Aldo-induced calcification of VSMCs. In conclusion, our study indicated that Aldo may induce vascular calcification related to chronic renal failure via the AIF-1 pathway which may provide a potential therapeutic target.

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Vascular Calcification in Rodent Models—Keeping Track with an Extented Method Assortment

Cited by 11 publications

References 145 publications

The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress

The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress

Role of endothelial CXCR4 in the development of aortic valve stenosis

The Role of AIF-1 in the Aldosterone-Induced Vascular Calcification Related to Chronic Kidney Disease: Evidence From Mice Model and Cell Co-Culture Model

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