Atherogenesis takes place in cholesterol-fed rabbits when circulating concentrations of endogenous cortisol are increased and inflammation suppressed.
Atherosclerosis is an inflammatory disease, but the response of the endogenous anti-inflammatory system during this process has not been evaluated previously. Cortisol is the end product of this anti-inflammatory system, but is also able to activate cellular processes that induce atherogenesis; however, it is unknown whether atherogenesis occurs when circulating concentrations of endogenous cortisol are increased or when they are decreased. We have evaluated the counter-regulatory responses of cortisol and interleukin-1beta (IL-1beta) during the short- and long-term responses to vascular injury in rabbits fed a 2% cholesterol diet. In the short-term group (n=18), serum cortisol and IL-1beta concentrations were measured after 10, 20 and 30 days. Rabbits developed hypercholesterolemia and hypercortisolemia, with only modest increases in IL-1beta. Although inflammation was low-grade, atherogenesis took place, with subintimal lipid accumulation evident on day 30. In the second group (n=18), we evaluated variables after 40, 60 and 90 days. This group developed hypercholesterolemia, but serum cortisol concentrations were inappropriately normal, while IL-1beta concentrations were elevated 8.6-fold; advanced atherosclerotic plaques were evident on days 60 and 90. These results show that atherogenesis occurs when high endogenous cortisol levels are suppressing inflammation, and are consistent with a promotion of early atherogenesis by high cortisol concentrations.
de Prada
Teresa Pérez
TP
Laboratory of Experimental Cardiology, Medicina y Cirugía Experimentales, Hospital Clínico San Carlos, Madrid, Spain.
Pozzi
Aranzazu Ortega
AO
Coronado
Mónica Torres
MT
Pounchard
Marie Anne
MA
Gonzalez
Pablo
P
Boscá
Lisardo
L
Fantidis
Panayotis
P
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D005487:Foam Cells / Q000473:pathology; D006854:Hydrocortisone / Q000097:blood*; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D007249:Inflammation / Q000097:blood / Q000209:etiology; D053583:Interleukin-1beta / Q000097:blood*; D011817:Rabbits; D013997:Time Factors
D002791:Cholesterol, Dietary; D053583:Interleukin-1beta; D002784:Cholesterol; D006854:Hydrocortisone