[en] 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.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Roosens, Bram
Droogmans, Steven
Hostens, Jeroen
Somja, Joan ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Stewart, B. F., Siscovick, D., Lind, B. K., Gardin, J. M., Gottdiener, J. S., Smith, V. E., et al. (1997). Clinical factors associated with calcific aortic valve disease. Cardiovascular health study. Journal of the American College of Cardiology, 29, 630-634. (Pubitemid 27116107)
Rosenhek, R. (2005). Statins for aortic stenosis. New England Journal of Medicine, 352, 2441-2443. (Pubitemid 40958444)
Taylor, A. J., Burke, A. P., O'Malley, P. G., Farb, A., Malcom, G. T., Smialek, J., et al. (2000). A comparison of the Framingham risk index, coronary artery calcification, and culprit plaque morphology in sudden cardiac death. Circulation, 101, 1243-1248. (Pubitemid 30158610)
Kawasaki, M., Takatsu, H., Noda, T., Ito, Y., Kunishima, A., Arai, M., et al. (2001). Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images. Journal of the American College of Cardiology, 38, 486-492. (Pubitemid 32721778)
Donnelly, K. B. (2008). Cardiac valvular pathology: comparative pathology and animal models of acquired cardiac valvular diseases. Toxicologic Pathology, 36, 204-217. (Pubitemid 351534488)
Zittermann, A., & Koerfer, R. (2008). Protective and toxic effects of vitamin D on vascular calcification: clinical implications. Molecular Aspects of Medicine, 29, 423-432.
Zittermann, A., Schleithoff, S. S., & Koerfer, R. (2007). Vitamin D and vascular calcification. Current Opinion in Lipidology, 18, 41-46. (Pubitemid 46090236)
Price, P. A., June, H. H., Buckley, J. R., & Williamson, M. K. (2001). Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 1610-1616. (Pubitemid 34215580)
Cardus, A., Panizo, S., Parisi, E., Fernandez, E., & Valdivielso, J. M. (2007). Differential effects of vitamin D analogs on vascular calcification. Journal of Bone and Mineral Research, 22, 860-866. (Pubitemid 351339746)
Price, P. A., Faus, S. A., & Williamson, M. K. (2000). Warfarin-induced artery calcification is accelerated bygrowth and vitamin D. Arteriosclerosis, Thrombosis, and Vascular Biology, 20, 317-327. (Pubitemid 30086086)
Droogmans, S., Franken, P. R., Garbar, C., Weytjens, C., Cosyns, B., Lahoutte, T., et al. (2007). In vivo model of drug-induced valvular heart disease in rats: pergolide-induced valvular heart disease demonstrated with echocardiography and correlation with pathology. European Heart Journal, 28, 2156-2162. (Pubitemid 47517444)
Weytjens, C., Cosyns, B., D'Hooge, J., Gallez, C., Droogmans, S., Lahoute, T., et al. (2006). Doppler myocardial imaging in adult male rats: reference values and reproducibility of velocity and deformation parameters. European Journal of Echocardiog-raphy, 7, 411-417. (Pubitemid 44645064)
Droogmans, S., Roosens, B., Cosyns, B., Degaillier, C., Hernot, S., Weytjens, C., et al. (2009). Dose dependency and reversibility of serotonin-induced valvular heart disease in rats. Cardiovascular Toxicology, 9, 134-141.
Ngo, D. T., Stafford, I., Kelly, D. J., Sverdlov, A. L., Wuttke, R. D., Weedon, H., et al. (2008). Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein. European Journal of Pharmacology, 590, 290-296.
Nightingale, A. K., & Horowitz, J. D. (2005). Aortic sclerosis: not an innocent murmur but a marker of increased cardiovascular risk. Heart, 91, 1389-1393. (Pubitemid 41531805)
Di Bello, V., Giorgi, D., Viacava, P., Enrica, T., Nardi, C., Palagi, C., et al. (2004). Severe aortic stenosis and myocardial function: diagnostic and prognostic usefulness of ultrasonic integrated backscatter analysis. Circulation, 110, 849-855. (Pubitemid 39096014)
McCollough, C. H., Ulzheimer, S., Halliburton, S. S., Shanneik, K., White,R.D., & Kalender, W. A.(2007). Coronary artery calcium: a multi-institutional, multimanufacturer international standard for quantification at cardiac CT. Radiology, 243, 527-538. (Pubitemid 46649710)
Callister, T. Q., Cooil, B., Raya, S. P., Lippolis, N. J., Russo, D. J., & Raggi, P. (1998). Coronary artery disease: improved reproducibility of calcium scoring with an electron-beam CT volumetric method. Radiology, 208, 807-814. (Pubitemid 28405121)
Shavelle, D. M., Budoff, M. J., Buljubasic, N., Wu, A. H., Takasu, J., Rosales, J., et al. (2003). Usefulness of aortic valve calcium scores by electron beam computed tomography as a marker for aortic stenosis. American Journal of Cardiology, 92, 349-353. (Pubitemid 36897731)
Messika-Zeitoun, D., Aubry, M. C., Detaint, D., Bielak, L. F., Peyser, P. A., Sheedy, P. F., et al. (2004). Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation, 110, 356-362. (Pubitemid 38955506)
Postnov, A. A., Vinogradov, A. V., Van Dyck, D., Saveliev, S. V., & De Clerck, N. M. (2003). Quantitative analysis of bone mineral content by X-ray microtomography. Physiological Measurement, 24, 165-178. (Pubitemid 36330463)
Ogle, M. F., Kelly, S. J., Bianco, R. W., & Levy, R. J. (2003). Calcification resistance with aluminum-ethanol treated porcine aortic valve bioprostheses in juvenile sheep. Annals of Thoracic Surgery, 75, 1267-1273. (Pubitemid 36399417)
Persy, V., Postnov, A., Neven, E., Dams, G., De Broe, M., D'Haese, P., et al. (2006). High-resolution X-ray microtomog-raphy is a sensitive method to detect vascular calcification in living rats with chronic renal failure. Arteriosclerosis, Thrombosis, and Vascular Biology, 26, 2110-2116. (Pubitemid 44253796)
van den Broek, F. A., Beems, R. B., van Tintelen, G., Lemmens, A. G., Fielmich-Bouwman, A. X., & Beynen, A. C. (1997). Co-variance of chemically and histologically analysed severity of dystrophic cardiac calcification in mice. Laboratory Animals, 31, 74-80. (Pubitemid 27075590)
Gaillard, V., Jover, B., Casellas, D., Cordaillat, M., Atkinson, J., & Lartaud, I. (2008). Renal function and structure in a rat model of arterial calcification and increased pulse pressure. Am J Physiol Renal Physiol, 295, F1222-F1229.
Lartaud-Idjouadiene, I., Lompre, A. M., Kieffer, P., Colas, T., & Atkinson, J. (1999). Cardiac consequences of prolonged exposure to an isolated increase in aortic stiffness. Hypertension, 34, 63-69. (Pubitemid 29325720)
Norman, P. E., & Powell, J. T. (2005). Vitamin D, shedding light on the development of disease in peripheral arteries. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 39-46. (Pubitemid 40054252)
Wong, C. Y., O'Moore-Sullivan, T., Leano, R., Byrne, N., Beller, E., & Marwick, T. H. (2004). Alterations of left ventricular myocardial characteristics associated with obesity. Circulation, 110, 3081-3087. (Pubitemid 39492002)
Khan, Z., Boughner, D. R., & Lacefield, J. C. (2008). Anisotropy of high-frequency integrated backscatter from aortic valve cusps. Ultrasound in Medicine and Biology, 34, 1504-1512.
Ngo, D. T., Wuttke, R. D., Turner, S., Marwick, T. H., & Horowitz, J. D. (2004). Quantitative assessment of aortic sclerosis using ultrasonic backscatter. Journal of the American Society of Echocardiography, 17, 1123-1130. (Pubitemid 39388903)
Ortlepp, J. R., Hoffmann, R., Ohme, F., Lauscher, J., Bleckmann, F., & Hanrath, P. (2001). The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart, 85, 635-638. (Pubitemid 32973456)
Drolet, M. C., Arsenault, M., & Couet, J. (2003). Experimental aortic valve stenosis in rabbits. Journal of the American College of Cardiology, 41, 1211-1217. (Pubitemid 36384911)
Drolet, M. C., Couet, J., & Arsenault, M. (2008). Development of aortic valve sclerosis or stenosis in rabbits: role of cholesterol and calcium. Journal of Heart Valve Disease, 17, 381-387.