FUNCTIONAL IMPROVEMENT PRECEDES STRUCTURAL REGRESSION OF ATHEROSCLEROSIS

Background Vasoconstrictor responses to serotonin are augmented in mon keys with diet-induced atherosclerosis and improve after 18 months of normal diet. We tested the hypothesis that functional improvement may occur early during regression, before evidence of structural improveme nt. Methods and Results Responses of the iliac artery to serotonin wer e measured by quantitative angiography and a Doppler flow probe in sev eral groups of monkeys: (1) normal monkeys, (2) monkeys fed an atherog enic diet for 2 years (atherosclerotic), and (3) monkeys fed an athero genic diet for 2 years (preregression) followed by a normal diet for 4 , 8, or 12 months (regression). In normal monkeys, serotonin produced minimal constriction of the iliac artery, and blood flow to the legs i ncreased. In atherosclerotic monkeys, there was pronounced constrictio n of the iliac artery, and blood flow to the legs decreased markedly. After 4 months of regression diet, four of eight monkeys demonstrated marked reduction in hyperresponsiveness to serotonin angiographically, and by 8 months, six of eight monkeys had significant improvement. Af ter regression, serotonin produced minimal changes in flow. There was no reduction in intimal area tie, atherosclerotic lesion) in iliac art eries from regression monkeys compared with atherosclerotic monkeys, b ut there was a marked reduction in cholesteryl ester in arteries from regression monkeys. Conclusions Abnormal vasoconstrictor responses to serotonin usually return to or toward normal within a few months durin g regression of atherosclerosis. Functional improvement occurs in conj unction with early resorption of lipid from the arterial wall and occu rs before detectable changes in mass of the atherosclerotic lesion.