Effects of dietary soy protein on iliac and carotid artery atherosclerosis and gene expression in male monkeys

Male cynomolgus macaques (n = 91) consumed an isoflavone (IF)-free, atherogenic control diet containing casein/lactalbumin for 5 months, then were randomized to three groups: control (n = 30) continued on the control diet; low IF (n = 30) received a mixture of unmodified and IF-depleted soy protein isolate (SPI) (0.94 mg IF/g protein, approximating a human intake of 75 mg/day); high IF (n = 31) received unmodified SPI (1.88 mg IF/g protein, approximating a human intake of 150 mg/day) for 31 months. Iliac and carotid artery atherosclerosis, and arterial and hepatic mRNA transcripts related to inflammation and estrogen receptors (ER) were measured. Trend analysis identified a significant inverse relationship between dietary IF content and plaque area in the iliac (p < 0.05) but not carotid arteries (p > 0.13). No significant effect of diet on inflammatory gene or estrogen receptor expression was observed. Plaque area was positively correlated with the mRNA transcript levels for arterial MCP-1, ICAM-1, and the macrophage marker CD68 (all r > 0.25, p < 0.03), and negatively correlated with ERα and ERβ (all r < −0.23, p < 0.03). Coronary artery plaque area appeared to be more closely associated with gene expression patterns of the iliac arteries than the carotid arteries. The data suggests benefits of dietary soy on atherosclerotic plaque development in males may be mediated through inflammation-independent pathways. The negative associations of arterial ERα expression with atherosclerosis lend support to a mechanistic role for estrogen receptors in atherosclerosis susceptibility which merits further study.