Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, 6200 MD Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands.
Int J Mol Sci. 2020 Jul 13;21(14):4944. doi: 10.3390/ijms21144944.
Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study ( = 674), underwent echocardiography. Serum MMPs (i.e., MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI); 0.03 (0.01; 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI; -0.04 (-0.07; -0.01) and -0.04 (-0.06; -0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI; 0.04 (0.00; 0.07, -interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI; -0.05 (-0.09; -0.01, -interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex.
细胞外基质蛋白的周转率可能在左心房（LA）重构中发挥重要作用。本研究旨在探讨基质金属蛋白酶（MMPs）、金属蛋白酶组织抑制剂（TIMP-1）与左心房容积指数（LAVI）之间的相关性，以及这些相关性是否独立于 TIMP-1 水平。来自 Hoorn 研究的参与者为一个基于人群的队列研究（=674），接受了超声心动图检查。使用 ELISA 法测量血清 MMPs（即 MMP-1、MMP-2、MMP-3、MMP-9 和 MMP-10）和 TIMP-1 水平。使用多元线性回归分析。MMP-1 水平与 LAVI 无关。较高的 MMP-2 水平与较大的 LAVI 相关（MMP 每标准差增加的回归系数（95%置信区间）；0.03（0.01；0.05）。较高的 MMP-3 和 MMP-9 水平与较小的 LAVI 相关；-0.04（-0.07；-0.01）和-0.04（-0.06；-0.02）。只有在女性中，较高的 MMP-10 水平与较大的 LAVI 相关；0.04（0.00；0.07，-交互作用 0.04）。此外，只有在女性中，较高的 TIMP-1 水平与较小的 LAVI 相关；-0.05（-0.09；-0.01，-交互作用 0.03）。MMP 与 LAVI 之间的相关性独立于 TIMP-1 水平。总之，血清 MMPs 与 LAVI 相关，独立于 CVD 危险因素和 TIMP-1 水平。此外，这些相关性根据性别和 MMP 亚组而有所不同。这表明 MMPs 在 LA 重构中的作用是复杂的。
