Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea.
Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, Gwangju, Republic of Korea; Center of Molecular Medicine, Graduate School, Chonnam National University, Republic of Korea.
Life Sci. 2014 Apr 17;101(1-2):15-26. doi: 10.1016/j.lfs.2014.02.009. Epub 2014 Feb 18.
We elucidated the therapeutic potential of human umbilical vein endothelial cells (HUVECs) for ameliorating progressive heart failure in a myocardial infarction (MI) rat model.
MI was induced by ligation of left anterior descending artery, and HUVEC was transplanted 1week after MI. Cardiac function was evaluated by echocardiography, and histological analyses were performed.
Phosphate-buffered saline (MI-V, n=5) or HUVEC (MI-HV, n=5) were injected into the border zone and infarcted area 7days after ligation of the left coronary artery in rats. The MI-HV group showed attenuation of left ventricular (LV) remodeling compared with the MI-V group. In the infarcted myocardium, a few of injected HUVEC was retained up to 28days. The ratios of matrix metalloproteinase (MMP)-2 or MMP-9 to tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-3 were decreased in the MI-HV group compared with the MI-V group. In vivo zymography analysis showed that HUVEC transplantation decreased the activities of MMP-2 and MMP-9. In immunohistochemistry, decreased MMP-2 and increased TIMP-1 and TIMP-3 expression were observed at 48h after HUVEC transplantation. These effects on MMP/TIMP balance were inhibited by L-NAME administration (an eNOS inhibitor, 10mg/kg). NOS inhibition decreased the protein expressions of TIMP-1 and TIMP-3 but did not change the protein expressions of MMP-2 and MMP-9.
Our data suggest that altered balance between MMP and TIMP by HUVEC transplantation contributed to attenuation of ventricular remodeling after MI via eNOS.
我们阐明了人脐静脉内皮细胞（HUVEC）在改善心肌梗死（MI）大鼠模型进行性心力衰竭中的治疗潜力。
结扎左前降支诱导 MI，MI 后 1 周移植 HUVEC。通过超声心动图评估心功能，并进行组织学分析。
磷酸盐缓冲盐水（MI-V，n=5）或 HUVEC（MI-HV，n=5）在结扎大鼠左冠状动脉 7 天后被注射到边界区和梗死区。与 MI-V 组相比，MI-HV 组左心室（LV）重构减弱。在梗死心肌中，注射的 HUVEC 中有少量保留至 28 天。与 MI-V 组相比，MI-HV 组基质金属蛋白酶（MMP）-2 或 MMP-9 与基质金属蛋白酶抑制剂（TIMP）-1 或 TIMP-3 的比值降低。体内酶谱分析显示，HUVEC 移植降低了 MMP-2 和 MMP-9 的活性。免疫组织化学显示，HUVEC 移植后 48 小时 MMP-2 减少，TIMP-1 和 TIMP-3 表达增加。NOS 抑制（一种 eNOS 抑制剂，10mg/kg）抑制了 MMP/TIMP 平衡的这些变化。NOS 抑制降低了 TIMP-1 和 TIMP-3 的蛋白表达，但不改变 MMP-2 和 MMP-9 的蛋白表达。
我们的数据表明，HUVEC 移植引起的 MMP 和 TIMP 平衡改变通过 eNOS 有助于 MI 后心室重构的减弱。
