Cevik Cihan, Nugent Kenneth, Meyerrose Gary, Otahbachi Mohammad, Izgi Cemil, Lyte Mark, Fish R David
Department of Adult Cardiology, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston, Texas 77030, USA.
Tex Heart Inst J. 2011;38(3):229-33.
Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13--an enzyme crucial to the initiation of collagen degradation-as part of their plaque-stabilizing effect.We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and low-density-lipoprotein cholesterol in 14 patients with hypercholesterolemia. All were at low risk for adverse cardiovascular events and were given 20 mg/d of rosuvastatin for 4 weeks. Post-therapy levels of matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 were compared with baseline levels. Although low-density-lipoprotein cholesterol levels were significantly decreased in the 14 patients (mean baseline level, 152 ± 21 mg/dL vs mean post-therapy level, 73 ± 45 mg/dL; P < 0.001), matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 levels were unchanged (matrix metalloproteinase-13, 0.295 ± 0.06 ng/mL vs 0.323 ± 0.11 ng/mL, P = 0.12; and tissue inhibitor of metalloproteinase-1, 400.8 ± 43.4 ng/mL vs 395.3 ± 47.5 ng/mL, P = 0.26). We conclude that even though there was a decrease in low-density-lipoprotein cholesterol, short-term, high-dose rosuvastatin therapy has no effect on matrix metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 levels in hypercholesterolemic patients. However, further investigation is warranted.
基质金属蛋白酶可降解动脉粥样硬化斑块中的胶原蛋白含量并降低斑块稳定性。在动脉粥样硬化斑块的组织切片中，基质金属蛋白酶的表达会增加。3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）通过减弱导致表达增加的炎症过程，降低动脉粥样斑块中基质金属蛋白酶-1、-2、-3和-9的组织表达。然而，尚不清楚他汀类药物是否会降低基质金属蛋白酶-13的水平（一种对胶原蛋白降解起始至关重要的酶），这是否是其斑块稳定作用的一部分。我们前瞻性地研究了他汀类药物治疗对14例高胆固醇血症患者血清基质金属蛋白酶-13、金属蛋白酶组织抑制剂-1和低密度脂蛋白胆固醇水平的影响。所有患者发生不良心血管事件的风险较低，并给予20mg/d的瑞舒伐他汀治疗4周。将治疗后基质金属蛋白酶-13和金属蛋白酶组织抑制剂-1的水平与基线水平进行比较。尽管14例患者的低密度脂蛋白胆固醇水平显著降低（平均基线水平为152±21mg/dL，治疗后平均水平为73±45mg/dL；P<0.001），但基质金属蛋白酶-13和金属蛋白酶组织抑制剂-1水平未发生变化（基质金属蛋白酶-13，0.295±0.06ng/mL对0.323±0.11ng/mL，P=0.12；金属蛋白酶组织抑制剂-1，400.8±43.4ng/mL对395.3±47.5ng/mL，P=0.26）。我们得出结论，尽管低密度脂蛋白胆固醇有所降低，但短期、高剂量的瑞舒伐他汀治疗对高胆固醇血症患者的基质金属蛋白酶-13和金属蛋白酶组织抑制剂-1水平没有影响。然而，有必要进行进一步的研究。
