Functional improvement precedes structural regression of atherosclerosis

Area of Science:

• Cardiovascular biology
• Vascular physiology
• Atherosclerosis research

Background:

• Diet-induced atherosclerosis in monkeys causes augmented vasoconstrictor responses to serotonin.
• These responses improve after prolonged normal diet (18 months).
• Hypothesis: Functional improvement may precede structural changes during early atherosclerosis regression.

Purpose of the Study:

• To investigate early functional improvements in vasoconstrictor responses during atherosclerosis regression.
• To determine if functional changes occur before structural improvements in atherosclerotic arteries.

Main Methods:

• Quantitative angiography and Doppler flow probe used to measure iliac artery responses to serotonin in normal, atherosclerotic, and regressing monkeys.
• Monkeys with atherosclerosis were fed a normal diet for 4, 8, or 12 months.
• Arterial intimal area and cholesteryl ester content were analyzed.

Main Results:

• Atherosclerotic monkeys showed pronounced iliac artery constriction and decreased blood flow in response to serotonin.
• Early regression (4-8 months) demonstrated significant improvement in hyperresponsiveness to serotonin.
• No reduction in atherosclerotic lesion size (intimal area) was observed, but cholesteryl ester levels decreased markedly.

Conclusions:

• Abnormal vasoconstrictor responses to serotonin normalize within months during atherosclerosis regression.
• Functional improvement correlates with early lipid resorption from the arterial wall.
• These functional changes precede detectable alterations in the atherosclerotic lesion's mass.