The effect of estrogen on T lymphocyte immunoregulation in mice with hypertrophic cardiomyopathy

Abstract

Objective To investigate the effect of the estrogenfor on T lymphocyte immunoregulation in mice with hypertrophic cardiomyopathy caused by AngⅡ. Methods Thirty one female C57BL/6 mice between 8~10 weeks were randomly divided into 4 groups: Sham (n=8), Sham+ AngⅡ (n=7), Ovx (n=8), Ovx+ AngⅡ (n=8). Osmotic mini-pumps containing AngⅡ (1000 ng·kg-1·d-1) were implanted subcutaneously in experimental mice. Thirty days after mini-pump implantation, blood pressure and heart rate were measured noninvasively in conscious animals by the tail-cuff method. Transthoracic echocardiography was performed under light sedation with 1.0% isoflurane. Ejection fraction(EF), fractional shortening(FS), diastolic/systolic ventricular septal (IVSd/IVSs) and posterior wall thickness (LVPWTd/LVPWTs), left ventricular diastolic and systolic volumes (LV VOLd/LV VOLs) were measured before and at the second, third, fourth, fifth week after the treatment. The immunologic markers of T cells CD3+ , CD4+ , CD8+ were analyzed by multicolor flow cytometry. Results The hypertension and hypertrophic cardiomyopathy model was set up in the mice by infusion of AngⅡ (1000 ng/kg per day). Each time point after modeling, Sham+ AngⅡ group showed significantly higher systolic blood pressure than in the sham group, Ovx+ AngⅡ group increased in systolic blood pressure compared with Ovx group. There were significant difference (F=15.23, P<0.01). Compared with the Sham group, Sham+ AngⅡ group indicated significantly increased IVSs, IVSd, LVPWs, LVPWd (t=3.81、7.74、3.87、7.73, P<0.01); Compared with Ovx, Ovx+ AngⅡ group showed significantly increased IVSs, IVSd, LVPWs, LVPWd and significantly reduced LV VOLs, LV VOLd (t=8.64、6.01、4.93、8.59、-2.16、-2.58, P<0.05 or 0.01). Compared to Sham and Ovx group, sham+ AngⅡ and Ovx+ AngⅡ group had the higher percentage of T cell ratios with reduced CD4+ and increased CD8+ cells (t=6.24、-4.85、7.70、-10.62、2.13、-11.04、11.11、-24.24, P<0.05 or 0.01); But compared with the sham+ Ang group, Ovx+ Ang group percentage of total T cells decrease with higher CD4+ ratio and lower CD8+ proportions (t=-2.78、3.37、-3.42、3.16, P<0.05 or 0.01). Conclusion Our studies shows that estrogen plays an important role in T cellimmunoregulationfor in AngⅡ-induced hypertrophic cardiomyopathy. Key words: Estrogen s; Angiotensin Ⅱ; Hypertension; Cardiomyopathy, hypertrophic; Mice