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Journal of Integrative Medicine: Volume 17, 2019   Issue 2,  Pages: 107-114

DOI: 10.1016/j.joim.2019.01.010
Original Experimental Research
Impact of high-fat diet and vitamin D3 supplementation on aortic stenosis establishment in waved-2 epidermal growth factor receptor mutant mice
1. Bérénice Colleville (Deparment of Biology, Institut National de la santé et de la Recherche Médicale, U1096 (Endothélium, Valvulopathies et Insuffisance Cardiaque), Normandie University, Unirouen, 76000 Rouen, France )
2. Nicolas Perzo (Deparment of Biology, Institut National de la santé et de la Recherche Médicale, U1096 (Endothélium, Valvulopathies et Insuffisance Cardiaque), Normandie University, Unirouen, 76000 Rouen, France )
3. Guillaume Avinée (Deparment of Biology, Institut National de la santé et de la Recherche Médicale, U1096 (Endothélium, Valvulopathies et Insuffisance Cardiaque), Normandie University, Unirouen, 76000 Rouen, France )
4. Ana?s Dumesnil (Deparment of Biology, Institut National de la santé et de la Recherche Médicale, U1096 (Endothélium, Valvulopathies et Insuffisance Cardiaque), Normandie University, Unirouen, 76000 Rouen, France )
5. Frederic Ziegler (Deparment of Biology, Institut national de la santé et de la recherche médicale, U1073 ( Nutrition, I nflammation et D ysfonction de l’axe I ntestin - C erveau ) , Normandie Univ ersity , Unirouen, 76000 Rouen, France )
6. Paul Billoir (Deparment of Biology, Institut N ational de la santé et de la R echerche M édicale, U1096 ( Endothélium, Valvulopathies et Insuffisance C ardiaque ) , Normandie Univ ersity , Unirouen, 76000 Rouen, France )
7. Hélène Eltchaninoff (Deparment of Biology, Institut N ational de la santé et de la R echerche M édicale, U1096 ( Endothélium, Valvulopathies et Insuffisance C ardiaque ) , Normandie Univ ersity , Unirouen, 76000 Rouen, France )
8. Vincent Richard (Deparment of Biology, Institut N ational de la santé et de la R echerche M édicale, U1096 ( Endothélium, Valvulopathies et Insuffisance C ardiaque ) , Normandie Univ ersity , Unirouen, 76000 Rouen, France )
9. Eric Durand (Deparment of Biology, Institut N ational de la santé et de la R echerche M édicale, U1096 ( Endothélium, Valvulopathies et Insuffisance C ardiaque ) , Normandie Univ ersity , Unirouen, 76000 Rouen, France )

Abstract
Objective:
The use of animal models of aortic stenosis (AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed; data have indicated that while aortic regurgitation (AR) is effectively induced, development of AS is rare. We aimed to evaluate the effect of high-fat diet (HFD) and vitamin D3 supplementation in this model.
Methods: HFD and subcutaneous vitamin D3 injections were initiated at the age of 6 weeks until the age of 6 (n = 16, 6-month treatment group) and 9 (n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis (calcium, 1,25(OH)2D3 and cholesterol), histology and immunohistochemistry (CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment (6 or 9 months).
Results: Total cholesterol and 1,25(OH)2D3 were significantly increased relative to the control group. HFD and vitamin D3 supplementation did result in improvements to the model, since AS was only detected in 6 (15.3%) mice (2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group.

Conclusion: These results suggest that HFD and vitamin D3 supplementation have no effect in the waved-2 mice model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.

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Please cite this article as:
Colleville B, Perzo N, Avinée G, Dumesnil A, Ziegler F, Billoir P, Eltchaninoff H, Richard V, Durand E. Impact of high -fat diet and vitamin D3 supplementation on aortic stenosis establishment in waved 2 epidermal growth factor receptor mutant mice. J Integr Med. 2019; Epub ahead of print.
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