Pulse Wave Velocity and Morphological Changes Associated with Early Atherosclerosis Progression in the Aortas of Cynomolgus Monkeys

To determine the time course of changes in arterial stiffness and corresponding morphology during atherosclerosis progression, we determined pulse wave velocity (PWV) in cynomolgus monkeys fed atherogenic (test) and control diets over an 18-month period. At 6-month intervals, thoracic and abdominal aortic PWVs were determined with a pressure transducer retracted down the aorta in 5 cm increments. Iliac artery PWV was determined from the abdominal aortic pressure to a noninvasive femoral pulse. Groups of individual cardiac cycles, triggered by the ECGs, were sampled on a computer and the velocities (PWV) of the pulse wave fronts were calculated. There was no significant difference between groups until 18 months when test animal PWVs in the thoracic (7.44 +/- 0.83 m X s-1) and abdominal (8.52 +/- 0.67 m X s-1) aorta were significantly greater than those of controls (5.02 +/- 0.51 and 6.24 +/- 0.53 m X s-1, respectively), indicating increased arterial stiffness. There was no change in iliac PWV, 10.96 +/- 0.74 m X s-1 for 18-month test compared with 9.44 +/- 0.89 m X s-1 for controls. Constant infusion of nitroprusside and noradrenaline lowered and raised blood pressure and PWV in all groups, and PWV changes due to drug-induced pressure changes were greater in atherosclerotic than in control arteries. Systolic pressure of 18-month test and pulse pressure of 12- and 18-month test groups were significantly greater than controls under all drug conditions, also indicating increased vessel stiffness. Morphometric evaluation of histological aortic cross sections revealed early, noncomplicated atherosclerosis showing gradual increases in the ratio of intimal to medial cross-sectional area in the thoracic (1.24 +/- 0.30 after 18 months) and abdominal (1.70 +/- 0.42 after 18 months) aortas, compared with control ratios of essentially zero. The fraction of the internal elastic lamina covered with atherosclerotic lesions, and maximal intimal thickness also showed significant increases during the test diet period. These data show that early atherosclerosis resulted in aortic but not iliac stiffening which was detected by increased PWV before development of significant stenotic lesions.