Impact of long-term hyper-homocysteinemia on cardiac remolding in hypertensive rats / 中华老年医学杂志

ABSTRACT

Objective To investigate the impact of hyper-homocystinemia (Hcy)on cardiac remolding in spontaneously hypertensive rat(SHR)and the protective effects of folic and vitamin B12 on the remolding.Methods The seven-week-old SHR were divided into four groups according to different diet for 20 weeks.The control group was fed a perfect compound diet without methionine,the methionine group was fed a perfect compound diet added with 2 ％ methionine,the treatment group was fed as that of methionine group,but added with vitamin B12 0.09 mg/(kg.d)and folate 4 mg/(kg.d)in the last 12 weeks,the mixture group was fed as that of methionine group in the first 8 weeks,and as that of control group.At the end of the intervention period,plasma levels of Hcy and matrix metalloprotease(MMP)-9 were measured.The blood pressure was detected by the non-invasive blood pressure sensing device.The cardiac structure and function were detected using echocardiography and invasive hemodynamic method.Picro-sirius red(PSR)staining was used to check the fibrosis in paraffin embedding ventricle section.Results Plasma levels of Hcy and MMP-9 were increased in the methionine group,while there was no significant difference in plasma levels of Hcy and MMP-9 among the treatment group,the mixture diet group and control group.Rats in methionine group had the largest heart weight among four groups,and systolic blood pressure was lower in methionine group than in the control group(P＜0.05).Compared with the other three groups,the methionine group showed that the left ventricular end-diastolic pressure(LVEDP)was increased and-dp/dt maxwas decreased.Meanwhile,LVEDP and-dp/dt m,x had no significant difference between the control group,treatment group and mixture group.The methionine group showed the most severe decrease in the left ventricular fractional shortening(LVFS)and +dp/dt While LVFS and + dp/dt max had no statistical significance between the treatment group and control groups,but the mixture group had lower LVFS and +dp/dt max values as compared with the control group(both P＜0.05).Perivascular fibrosis was increased significantly in methionine group as compared with the other three groups,while the treatment and control groups had similar perivascular fibrosis,but the mixture group had higher perivascular fibrosis than did the control group,and had similar perivascular fibrosis to the treatment group.Fibrosis deposition in myocardium mesenchymal was similar to those observed in perivascular fibrosis,but the treatment group showed a more improvement of collagen deposition as compared with the mixture group.Conclusions Hyper-homocystinemia can accelerate systolic and diastolic dysfunction through accumulating fibrosis in myocardium and perivascular wall which lead to adverse cardiac remolding.Folate and vitamin B12 have protective effects on heart function by reversing the adverse changes through decreasing Hcy level.