Female cynomolgus monkeys are excellent models for understanding
cardiovascular disease and the relationships between inflammatory processes and conditions such as
atherogenesis. This review summarizes published research findings obtained through comprehensive, multidisciplinary, multi-investigator studies in nonhuman primates over the past two decades. These studies examined the effects of exogenous
estrogens and dietary
soy protein/
isoflavones (IFs) on
atherosclerosis, circulating
biomarkers, and tissue
inflammation in pre- and postmenopausal female cynomolgus monkeys.
Inflammation may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating and tissue
biomarkers with inflammatory and anti-inflammatory characteristics (including adhesion molecules such as
e-selectin, VCAM-1, and ICAM-1,
chemokines such as MCP-1,
cytokines such as
interleukins, and
acute phase reactants such as CRP, and others) may be useful indicators of disease status. Treatment of postmenopausal subjects with
estrogen resulted in significant reductions in several key inflammatory mediators as well as
atherosclerosis, while dietary IF had a more limited effect on
inflammation and
atherogenesis. Circulating concentrations of key inflammatory
proteins, including
monocyte-chemoattractant protein-1 (MCP-1) and
interleukin-6 (IL-6), were associated with
atherosclerosis and lesion characteristics in these animals. In premenopausal female monkeys, a diet enriched in
soy protein reduced
arterial inflammation as well as
atherogenesis in comparison to a diet enriched in
casein-
lactalbumin. Expression levels of
arterial inflammation associated genes (MCP-1, ICAM-1) and markers for inflammatory cell types (macrophages and T cells) correlated with plaque size, were differentially influenced by treatments, and represent potential targets for interventions. Arterial expression of
estrogen receptor alpha, the key mediator of
estrogenic effects, was inversely correlated with plaque size and indices of
inflammation, suggestive of an atheroprotective role. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic
disease progression and responses to treatment in female primates, and that
estrogens and dietary soy may inhibit
atherogenesis in part through anti-inflammatory mechanisms.