Abstract 130: CD4 T Cell Dysfunction Induced to Endothelial Apoptosis in Peri-menopausal Women with Low Estrogen levels
Background: Plaque erosion is responsible for the majority of acute coronary thrombi and induces acute coronary syndromes (ACS) in perimenopausal women. However, the causal relationship between low estrogen levels and plaque erosion mechanism in perimenopausal women is not fully understood. We examined whether perimenopausal women (PMW) with low levels of estrogen have had T cell dysfunction, and whether they experienced accelerated plaque erosion as a result.
Methods and Results: Fresh CD4 T cells were isolated from 45 PMW within 5 years after menopause (mean age 53.9 ± 6.0 years) and 40 women with regular menstruation cycles (NC, mean age 34.0 ± 7.4 years). Estrogen levels in plasma were lower in PMW than NC (P < 0.0001). Estrogen receptor α (ESR1) and estrogen receptor β (ESR2) mRNA of CD4 T cells in PMW were lower compared to NC by real time PCR (P < 0.05). Estrogen levels correlated significantly with ESR1 transcripts (R = 0.537, P < 0.03). The inflammation marker of hsCRP was higher (P < 0.003) and CD69, an activation marker of T cells, had stronger expression on CD4 T cells from PMW by FACS (P < 0.04). Measurement of fragmentation of DAPI-binding nuclear proteins showed that CD4 T cells from PMW induce significant human umbilical vein endothelial cells (HUVEC) apoptosis compared to those from NC (P < 0.001). Furthermore, CD4 T cells from PMW expressed strong p-selectin glycoprotein ligand-1(PSGL-1) and integrin (CD18) but not L-selectin by FACS (P < 0.006, P < 0.05, n.s., respectively). Estrogen levels correlated negatively with PSGL-1 (R = 0.997, P < 0.05) and CD4 T cell-induced HUVEC apoptosis (R = 0.439, P < 0.0001). Treatment with 17β-estradiol showed reduction of CD4 T cell-induced apoptosis in PMW. Estrogen receptor antagonist ICI 172,780 abolished estrogen protection.
Conclusions: From these results, we concluded that CD4 T cells in perimenopausal women were already activated and displayed dysfunctions related to deficiency of estrogen and estrogen receptors, which may be a factor that contributes to the acceleration of plaque erosion in atherosclerotic plaque and acute coronary syndromes.