Samnegård A, Silveira A, Tornvall P, Hamsten A, Ericsson C-G, Eriksson P
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
J Intern Med. 2006 May;259(5):530-6. doi: 10.1111/j.1365-2796.2006.01632.x.
The importance of matrix metalloproteinases (MMPs) in the progression and rupture of the atherosclerotic plaque is gaining increasing recognition but the mechanisms are not yet fully understood. The aim of this study was to investigate the significance of MMP-3 in the acute phase of myocardial infarction (MI) and the influence of the -1612 5A/6A MMP-3 gene promoter polymorphism on serum MMP-3 concentration.
One-hundred and sixty-four patients admitted with ST-elevation MI and receiving thrombolysis treatment were included in this study. Serum MMP-3 was analysed at admission, after 48 h and at 3 months.
Serum MMP-3 concentration was significantly increased at 3 months when compared with admission and 48 h (19.5 ng mL(-1) [14.4-24.7] vs. 15.5 ng mL(-1) [10.5-21.8] at admission, P < 0.001; and 14.7 ng mL(-1) [9.9-23.8] at 48 h, P < 0.001). Furthermore, we found the -1612 5A/6A polymorphism to influence the serum concentration of MMP-3 at all time-points: 14.1 ng mL(-1) [10.2-18.8] in 5A/5A; 19.6 ng mL(-1) [15.0-24.4] in 5A/6A; and 24.0 ng mL(-1) [20.1-32.3] in 6A/6A genotype at 3 months (P < 0.001 between all groups). Female patients had lower serum MMP-3 concentration than male patients at all time-points (14.8 ng mL(-1) [9.4-20.8] vs. 19.9 ng mL(-1) [16.0-26.9], P < 0.0001 at 3 months).
Serum concentration of MMP-3 is significantly lower in the acute stage of MI than during recovery and is significantly influenced by -1612 5A/6A genotype and gender. Together with previous findings, these results primarily implicate MMP-3 in atherosclerosis progression rather than in acute MI.
基质金属蛋白酶(MMPs)在动脉粥样硬化斑块进展和破裂中的重要性日益受到认可,但其机制尚未完全明确。本研究旨在探讨MMP - 3在心肌梗死(MI)急性期的意义以及 - 1612 5A/6A MMP - 3基因启动子多态性对血清MMP - 3浓度的影响。
本研究纳入了164例因ST段抬高型心肌梗死入院并接受溶栓治疗的患者。在入院时、48小时后及3个月时对血清MMP - 3进行分析。
与入院时和48小时相比,3个月时血清MMP - 3浓度显著升高(入院时为15.5 ng/mL [10.5 - 21.8],3个月时为19.5 ng/mL [14.4 - 24.7],P < 0.001;48小时时为14.7 ng/mL [9.9 - 23.8],P < 0.001)。此外,我们发现 - 1612 5A/6A多态性在所有时间点均影响血清MMP - 3浓度:3个月时,5A/5A基因型为14.1 ng/mL [10.2 - 18.8];5A/6A基因型为19.6 ng/mL [15.0 - 24.4];6A/6A基因型为24.0 ng/mL [20.1 - 32.3](所有组间P < 0.001)。在所有时间点,女性患者的血清MMP - 3浓度均低于男性患者(3个月时,女性为14.8 ng/mL [9.4 - 20.8],男性为19.9 ng/mL [16.0 - 26.9],P < 0.0001)。
MI急性期血清MMP - 3浓度显著低于恢复期间,且受 - 1612 5A/6A基因型和性别的显著影响。结合先前的研究结果,这些结果主要表明MMP - 3与动脉粥样硬化进展有关,而非急性心肌梗死。