A mini-review on quantification of atherosclerosis in hypercholesterolemic mice
Atherosclerosis is a leading cause of morbidity and mortality in many countries. Mice are the most frequently used animal model to study the pathogenesis and molecular mechanisms of atherosclerosis. En face analyses of the aorta and cross-sections of the aortic root are the two common modes for quantifying the severity of atherosclerosis in mice. This mini-review introduces these two methods, discusses their pros and cons, and provides suggestions to optimize the quantification of atherosclerosis, thereby enhancing rigor and reproducibility in preclinical research.
Daugherty A, Tall AR, Daemen M, et al., 2017, Recommendation on design, execution, and reporting of animal atherosclerosis studies: A scientific statement from the American heart association. Arterioscler Thromb Vasc Biol, 37: e131–e157. https://doi.org/10.1161/atv.0000000000000062
Wu C, Daugherty A, Lu HS, 2019, Updates on approaches for studying atherosclerosis. Arterioscler Thromb Vasc Biol, 39: e108–e117.
Lu H, Daugherty A, 2015, Atherosclerosis. Arterioscler Thromb Vasc Biol, 35: 485–491.
Lu H, Howatt DA, Balakrishnan A, et al., 2016, Hypercholesterolemia induced by a PCSK9 gain-of-function mutation augments angiotensin II-induced abdominal aortic aneurysms in C57BL/6 mice. Arterioscler Thromb Vasc Biol, 36: 1753–1757. https://doi.org/10.1161/atvbaha.116.307613
Roche-Molina M, Sanz-Rosa D, Cruz FM, et al., 2015, Induction of sustained hypercholesterolemia by single adeno-associated virus-mediated gene transfer of mutant hPCSK9. Arterioscler Thromb Vasc Biol, 35: 50–59. https://doi.org/10.1161/atvbaha.114.303617
Somanathan S, Jacobs F, Wang Q, et al., 2014, AAV vectors expressing LDLR gain-of-function variants demonstrate increased efficacy in mouse models of familial hypercholesterolemia. Circ Res, 115: 591–599. https://doi.org/10.1161/circresaha.115.304008
Goettsch C, Hutcheson JD, Hagita S, et al., 2016, A single injection of gain-of-function mutant PCSK9 adeno-associated virus vector induces cardiovascular calcification in mice with no genetic modification. Atherosclerosis, 251: 109–118. https://doi.org/10.1016/j.atherosclerosis.2016.06.011
Bjorklund MM, Hollensen AK, Hagensen MK, et al., 2014, Induction of atherosclerosis in mice and hamsters without germline genetic engineering. Circ Res, 114: 1684–1689. https://doi.org/10.1161/circresaha.114.302937
Daugherty A, Tabas I, Rader DJ, 2015, Accelerating the pace of atherosclerosis research. Arterioscler Thromb Vasc Biol, 35: 11–12. https://doi.org/10.1161/atvbaha.114.304833
Paigen B, Morrow A, Brandon C, et al., 1985, Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis, 57: 65–73. https://doi.org/10.1016/0021-9150(85)90138-8
Virmani R, Kolodgie FD, Burke AP, et al., 2000, Lessons from sudden coronary death: A comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol, 20: 1262–1275. https://doi.org/10.1161/01.atv.20.5.1262
Yla-Herttuala S, Bentzon JF, Daemen M, et al., 2011, Stabilisation of atherosclerotic plaques. Position paper of the European society of cardiology (ESC) working group on atherosclerosis and vascular biology. Thromb Haemost, 106: 1–19. https://doi.org/10.1160/th10-12-0784
Lu H, Rateri DL, Daugherty A, 2007, Immunostaining of mouse atherosclerosis lesions. Methods Mol Med, 139: 77–94. https://doi.org/10.1007/978-1-59745-571-8_4