Altered Compliance and Residual Strain Precede Angiographically Detectable Early Atherosclerosis in Low-Density Lipoprotein Receptor Deficiency

Abstract

Background This study was performed to detect changes in vascular biomechanical properties early in atherogenesis. Methods and Results Age- and weight-matched LDL-receptor deficient Watanabe hypercholesterolemic male rabbits (Group I: n=11) and normal rabbits (Group II: n=11) were studied. Fasting plasma lipoprotein concentrations, aortic angiography and intravascular ultrasound, in vivo aortic compliance evaluation, ex vivo aortic residual strain measurements, aortic lipid content and histopathology were determined. Plasma cholesterol was increased 9.8 fold and aortic cholesterol content was increased from 20 to 43 fold in Group I compared to Group II, respectively ( P <.00005). Angiography revealed no stenoses in either group, whereas intravascular ultrasound and histological studies of Group I showed small circumferential plaques with <10% cross-sectional area involvement. The residual strain in Group I was significantly increased in the ascending thoracic aorta (22.1±6.9% versus 10.4±3.2% in Group II, P <.0001), descending thoracic aorta (15.7±7.2% versus 4.8±1.3% in Group II, P <.0001), and abdominal aorta (18.0±4.8% versus 8.3±6.3% in Group II, P <.005). Changes in residual strain were inversely correlated with the aortic cholesterol content in the ascending thoracic aorta ( r =−.72; P =−.001), descending thoracic aorta ( r =−.95; P <.001), and abdominal aorta ( r =−.51; P =.019). Conclusions Early atherosclerosis in LDL-receptor deficient rabbits, undetectable by angiography yet observed by intravascular ultrasound imaging and histology, is associated with marked changes in ex vivo residual strain. Alterations in vascular biomechanical properties, associated with changes in cholesterol content, may have physiologic consequences and may be useful in detecting and quantitating early atherosclerosis.