Our previous studies demonstrated the morphological heterogeneity of e
ndothelial cells (ECs) and the emergence of large multinucleated ECs i
n human and animal atherosclerotic lesions. To investigate the functio
nal alteration of ECs in diet-induced atherosclerosis, immunoreactive
endothelin-1 (irET-1) release by ECs of the rabbit aorta was correlate
d with scanning electron microscopy. Rabbits were fed a cholesterol di
et for 12 weeks: by scanning electron microscopy, the area of ECs in t
he aorta increased in the hypercholesterolemic (HC) group as atheroscl
erosis progressed. Cultured ECs of the HC group released significantly
more irET-1 than ECs of the control. The plasma irET-1 level was also
elevated in the HC group. The results obtained suggest that accelerat
ed secretion of ET-1 by ECs contributes to the development of atherosc
lerotic vascular lesions.