Vitamin D2 supplementation induces the development of aortic stenosis in rabbits: Interactions with endothelial function and thioredoxin-interacting protein

Ngo, D.; Stafford, Irene; Kelly, Darren J.; Sverdlov, Aaron L.; Wuttke, Ronald D.; Weedon, Helen; Nightingale, Angus K; Rosenkranz, A; Smith, Malcolm D.; Chirkov, Yuliy Y.; Kennedy, Jennifer A.; Horowitz, John D.

doi:10.1016/j.ejphar.2008.05.051

Cited by 36 publications

(36 citation statements)

References 31 publications

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“…There were similar findings in rabbits, where stenosis could only be induced by combining an atheromatous and a calcifying factor [32]. Drolet and Ngo reported that a combination of high cholesterol and vitamin D 3 supplementation seems to be necessary to induce valve stenosis, whereas hypercholesterolemia or vitamin D alone only lead to sclerosis or calcifications without valvular stenosis [14,33].…”

Section: Discussionmentioning

confidence: 54%

“…As previously reported [13], fractional area change (FAC) was calculated by using the LV cross-sectional area at end diastole (LVAd) and at end systole (LVAs), with the fol- For quantification of cardiovascular calcifications, we characterized the tissue by analyzing the IB of tissue Doppler ultrasound reflectivity [14,15]. IB values were calculated automatically from the average power of the ultrasound backscattered signal [4].…”

Section: Left Ventricular (Lv) and Aortic Valve (Av) Functionmentioning

confidence: 99%

“…Blood pools: BP1 of the atrial cavity, BP2 of the left ventricular outflow tract, BP3 of the aortic lumen, BP4 of the left ventricular cavity. The positions of the ROIs were within the same region for all animals and during all cardiac cycles [4,14]. IB values for each ROI were acquired and averaged over 3 cycles.…”

Section: Left Ventricular (Lv) and Aortic Valve (Av) Functionmentioning

confidence: 99%

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Integrated Backscatter for the In Vivo Quantification of Supraphysiological Vitamin D3-Induced Cardiovascular Calcifications in Rats

et al. 2011

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Cardiovascular calcifications are frequently found in the aging population and are independent predictors of future cardiovascular events. Integrated backscatter (IB) of ultrasound reflectivity can easily quantify calcifications. For this purpose, 30 male Wistar rats received 25,000 IU/kg/day of vitamin D(3) (group 1, n = 8), 18,800 IU/kg/day (group 2, n = 8), or injections with the vehicle only (group 3, n = 14), for 10 weeks. Echocardiographic calibrated IB (cIB) was measured and calculated at baseline and after 10 weeks, followed by ex vivo micro-CT and histopathology of the aortic valve, ascending aorta, and myocardium. After 10 weeks, the mean cIB value of the aortic valve was significantly higher for vitamin D(3)-dosed animals compared to controls. The mean cIB value of the ascending aorta and the myocardium was also significantly higher in group 1 compared to group 3. In vivo IB results were confirmed by ex vivo micro-CT and histopathology. In conclusion, IB is a non-ionizing, feasible, and reproducible tool to quantify cardiovascular calcifications in an in vivo rat model. The integration of IB in the standard echocardiographic examination for the quantification of cardiovascular calcifications could be useful for serial evaluation of treatment efficacy and for prognosis assessment.

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Section: Discussionmentioning

confidence: 54%

Section: Left Ventricular (Lv) and Aortic Valve (Av) Functionmentioning

confidence: 99%

Section: Left Ventricular (Lv) and Aortic Valve (Av) Functionmentioning

confidence: 99%

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Integrated Backscatter for the In Vivo Quantification of Supraphysiological Vitamin D3-Induced Cardiovascular Calcifications in Rats

et al. 2011

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“…The standard rabbit model is the New Zealand white rabbit (NZWR) with a starting weight of 1.6–3 kg [74, 76–86] and hypercholesterolemia induced by one of four main diet categories (1) moderate-to-high cholesterol with [75–77, 81] or without fat [78, 79, 84, 85, 95, 103]; (2) moderate cholesterol and VitD2 [19, 80, 82]; (3) low cholesterol [74, 83, 86]; or (4) VitD2 only [82, 98]. (Below, rabbit diet additions are expressed as additional weight percentage added.)…”

Section: Animal Models Of Cavdmentioning

confidence: 99%

Animal Models of Calcific Aortic Valve Disease

Sider

Blaser

Simmons

2011

International Journal of Inflammation

106

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Calcific aortic valve disease (CAVD), once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

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“…The data regarding vitamin D supplementation and endothelial dysfunction have not been entirely consistent as one study in rabbits reported that vitamin D 2 supplementation actually caused endothelial dysfunction and increased levels of oxidative stress [15]. The relationships of 25-hydroxyvitamin D (25-OH D) and PTH to levels of NO metabolites (NOx) and oxidative stress in African-Americans have not been established.…”

Section: Introductionmentioning

confidence: 94%

Vitamin D and Parathyroid Hormone Relationships with Urinary Nitric Oxide Metabolites and Plasma Isoprostanes in African-Americans

Valina-Toth

Lai²,

Zhang³

et al. 2012

Cardiorenal Med

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Background: Vitamin D deficiency and secondary rises in parathyroid hormone (PTH) are highly prevalent in obese African-Americans. Endothelial dysfunction related to oxidative stress is more common in African-Americans compared to whites. Currently, the association of vitamin D (25-hydroxyvitamin D, 25-OH D) and PTH to nitric oxide metabolites (NOx) – nitrate and nitrite – and oxidative stress in African-Americans is unknown. Objective: A cross-sectional design was utilized to determine the association of 25-OH D and PTH with urinary NOx (UNOx) (n = 101) and plasma isoprostanes (n = 125), an oxidative stress marker, in overweight (body mass index of 25–39.9), normotensive African-Americans aged ≥35 years. Measurements: Multivariable linear regression analysis adjusted for age, sex, body mass index, and season was used to determine the relationship of 25-OH D and PTH to UNOx and isoprostanes. General linear models, adjusted for the same covariates, contrasted UNOx across three mutually exclusive vitamin D/PTH groups: (1) normal 25-OH D (51–249 nmol/l) and normal PTH (≤65 pg/ml); (2) low 25-OH D and normal PTH, and (3) low 25-OH D and high PTH. Results: 25-OH D was directly associated with UNOx before (p = 0.02) and after (p = 0.03) adjustment for PTH levels. A borderline significant association was observed between PTH and isoprostanes (p = 0.08). UNOx was 424, 290, and 270 µmol/8 h, respectively, across vitamin D/PTH groups 1–3 (p = 0.08). Conclusion: 25-OH D was directly associated with NO availability and PTH was positively, though borderline, associated with isoprostanes in overweight, normotensive adult African-Americans.

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Vitamin D2 supplementation induces the development of aortic stenosis in rabbits: Interactions with endothelial function and thioredoxin-interacting protein

Cited by 36 publications

References 31 publications

Integrated Backscatter for the In Vivo Quantification of Supraphysiological Vitamin D3-Induced Cardiovascular Calcifications in Rats

Integrated Backscatter for the In Vivo Quantification of Supraphysiological Vitamin D3-Induced Cardiovascular Calcifications in Rats

Animal Models of Calcific Aortic Valve Disease

Vitamin D and Parathyroid Hormone Relationships with Urinary Nitric Oxide Metabolites and Plasma Isoprostanes in African-Americans

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