PRECLINICAL STUDY
A High Fat/High Carbohydrate Diet Induces Aortic Valve Disease in C57BL/6J Mice
Marie-Claude Drolet, MS*,
Elise Roussel, MS*,
Yves Deshaies, PhD ,
Jacques Couet, PhD*,* and
Marie Arsenault, MD*
* Groupe de recherche en valvulopathies, Institut de cardiologie de Québec, Québec, Canada
Département d’anatomie et de physiologie, Faculté de médecine, Centre de recherche Hôpital Laval, Université Laval, Sainte-Foy, Québec, Canada.
Manuscript received June 30, 2005;
revised manuscript received September 16, 2005,
accepted September 26, 2005.
* Reprint requests and correspondence: Dr. Jacques Couet, Centre de recherche Hôpital Laval, 2527 Chemin Sainte-Foy, Sainte-Foy, Québec, Canada G1V 4G5. (Email: jacques.couet{at}med.ulaval.ca).
OBJECTIVES: The purpose of this study was to compare aortic valve function and morphology in adult wild-type (WT) mice and in low-density lipoprotein receptor-deficient (LDLr–/–) mice fed or not fed a high-fat/high-carbohydrate (HF/HC) diet.
BACKGROUND: Observations suggest a link between degenerative aortic valve stenosis (AS) and atherosclerosis. Aortic valve stenosis has been successfully induced in animal models of extreme hypercholesterolemia, but these models are less relevant to humans. It is not known if a proatherogenic HF/HC diet without added cholesterol could have the same negative impacts.
METHODS: Forty C57BL/6J mice were divided into four groups: WT + normal diet, WT + HF/HC diet, LDLr–/– with a normal diet, and LDLr–/– with a HF/HC diet. Aortic valve function and histology were evaluated by echocardiography after four months.
RESULTS: Wild-type mice on a HF/HC diet became mildly hypercholesterolemic, obese, and hyperglycemic. As expected, LDLr–/– mice became severely hypercholesterolemic. Both WT and LDLr–/– mice on a HF/HC diet displayed smaller valve areas and higher transvalvular velocities (p < 0.01) after four months. Aortic valve leaflets were thicker and infiltrated with lipids and macrophages in both HF/HC groups.
CONCLUSIONS: A HF/HC diet in mice results in significant aortic valve abnormalities. Putting WT mice on a HF/HC diet reproduced a combination of atherogenic factors (obesity, mild dyslipidemia, and hyperglycemia) more commonly encountered in humans than isolated severe hypercholesterolemia. Severe hypercholesterolemia was not a prerequisite in our model. This experimental model suggests that AS development is multifactorial and that hypercholesterolemia should not be the only target in this disease.
|
Abbreviations and Acronyms
| | AS = aortic valve stenosis | | AVA = aortic valve area | | HF/HC = high fat/high carbohydrate | | LDLr–/– = low-density lipoprotein receptor-deficient | | WT = wild type |
|
This article has been cited by other articles:
|
|
|
|
 
M. Shuvy, S. Abedat, R. Beeri, H. D. Danenberg, D. Planer, I. Z. Ben-Dov, K. Meir, J. Sosna, and C. Lotan
Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats
Cardiovasc Res,
August 1, 2008;
79(3):
492 - 499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Helske, T. Miettinen, H. Gylling, M. Mayranpaa, J. Lommi, H. Turto, K. Werkkala, M. Kupari, and P. T. Kovanen
Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves
J. Lipid Res.,
July 1, 2008;
49(7):
1511 - 1518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Demer and Y. Tintut
Vascular Calcification: Pathobiology of a Multifaceted Disease
Circulation,
June 3, 2008;
117(22):
2938 - 2948.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. B. Hinton Jr., C. M. Alfieri, S. A. Witt, B. J. Glascock, P. R. Khoury, D. W. Benson, and K. E. Yutzey
Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult
Am J Physiol Heart Circ Physiol,
June 1, 2008;
294(6):
H2480 - H2488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. B. Donnelly
Cardiac Valvular Pathology: Comparative Pathology and Animal Models of Acquired Cardiac Valvular Diseases
Toxicol Pathol,
February 1, 2008;
36(2):
204 - 217.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mohty, P. Pibarot, J.-P. Despres, C. Cote, B. Arsenault, A. Cartier, P. Cosnay, C. Couture, and P. Mathieu
Association Between Plasma LDL Particle Size, Valvular Accumulation of Oxidized LDL, and Inflammation in Patients With Aortic Stenosis
Arterioscler. Thromb. Vasc. Biol.,
January 1, 2008;
28(1):
187 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Aikawa, M. Nahrendorf, J.-L. Figueiredo, F. K. Swirski, T. Shtatland, R. H. Kohler, F. A. Jaffer, M. Aikawa, and R. Weissleder
Osteogenesis Associates With Inflammation in Early-Stage Atherosclerosis Evaluated by Molecular Imaging In Vivo
Circulation,
December 11, 2007;
116(24):
2841 - 2850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Aikawa, M. Nahrendorf, D. Sosnovik, V. M. Lok, F. A. Jaffer, M. Aikawa, and R. Weissleder
Multimodality Molecular Imaging Identifies Proteolytic and Osteogenic Activities in Early Aortic Valve Disease
Circulation,
January 23, 2007;
115(3):
377 - 386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Weiss, M. Ohashi, J. D. Miller, S. G. Young, and D. D. Heistad
Calcific Aortic Valve Stenosis in Old Hypercholesterolemic Mice
Circulation,
November 7, 2006;
114(19):
2065 - 2069.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. O'Brien
Pathogenesis of Calcific Aortic Valve Disease: A Disease Process Comes of Age (and a Good Deal More)
Arterioscler. Thromb. Vasc. Biol.,
August 1, 2006;
26(8):
1721 - 1728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
