Novel insights into coronary lumen preservation during progression of coronary atherosclerosis in coronary atherosclerosis-prone rabbits

In Brief Background In coronary atherosclerosis-prone Watanabe heritable hyperlipidaemic (WHHLCA) rabbits, an animal model for low-density lipoprotein receptor deficiency and spontaneous coronary atherosclerosis, the coronary arteries show compensatory remodelling during the progression of atherosclerosis. Therefore, we analysed coronary remodelling of WHHLCA rabbits quantitatively using a method that eliminates the limitations of previous analytical methods. Methods Arterial remodelling was evaluated in perfusion-fixed coronary arteries of 11 WHHLCA rabbits using both new and previous analyses. With the improved methods removing limitations on quantitative analysis of arterial remodelling, we evaluated how lumen area or arterial size changed with accumulating atherosclerotic plaques compared to before plaque development. The original lumen area before plaque development was calculated using the diameter-length relationship. Wall shear stress change ratio was calculated from changes in arterial size. Results Using the old analytical method (and as seen in similar human studies), lumen area increased up to a level of 29% of cross-sectional narrowing. However, with the improved analysis, in cross-sectioning narrowing at levels below 10%, the lumen area modestly decreased, and when the cross-sectional narrowing ranged from 10–68%, the lumen area remained constant, and diminished sharply despite continued remodelling when cross-sectional narrowing reached 70% or above. Arterial remodelling progressed quantitatively to a slight increase in arterial wall shear stress as well as lumen area up to a level of 70% cross-sectional narrowing. Conclusions These findings demonstrate marked influences of arterial tapering and individual variation of arterial size on quantitative analysis of arterial remodelling, and provide the novel insight that coronary compensatory remodelling in atherosclerosis maintains the lumen size up to levels of 70% cross-sectional narrowing in proportion to wall shear stress. Prior quantitative analysis of coronary artery compensatory remodeling is limited by individual variation of arterial size and arterial tapering. Therefore, we developed a new analytical method resolving this limitation and analyzed coronary compensatory remodeling using perfusion-fixed coronary arteries of WHHL rabbits, an animal model for spontaneous coronary atheroscl erosis. In the new anal ysis, we evaluated how lumen area or arterial size was changed with accumulating atherosclerotic plaques compared to before plaque developed. The lumen area modestly decreased below 10% cross-sectional narrowing (CSN), remained constant from 10% to 68% CSN, and diminished sharply despite continued remodeling above 70% CSN. Up to 70% CSN, arterial remodeling progressed quantitatively to maintain constant arterial wall shear stress as well as lumen area. Quantitative anal ysis eliminating the previous limitation provides the novel insight that coronary compensatory remodeling in atherosclerosis maintains lumen size up to 70% CSN in proportion to wall shear stress.