Institute of Clinical Physiology CNR, Via G. Moruzzi 1, Pisa, Italy.
Sant'Anna School of Advanced Studies, Piazza Martiri della Libertà, 33, Pisa, Italy.
Vascul Pharmacol. 2022 Oct;146:107098. doi: 10.1016/j.vph.2022.107098. Epub 2022 Sep 12.
MMP-9 is a predictor of atherosclerotic plaque instability and adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression and the related molecular basis in stable patients with chronic coronary syndrome (CCS).
MMP9 serum levels were measured in 157 CCS patients (58 ± 8 years of age; 66% male) undergoing coronary computed tomography angiography at baseline and after a follow up period of 6.5 ± 1.1 years to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volumes (PV). Gene expression analysis was evaluated in whole blood using a transcriptomic approach by RNA-seq.
At multivariate analysis, serum MMP9 was associated with annual change of Total and Necrotic Core PV (Coefficient 3.205, SE 1.321, P = 0.017; 1.449, SE 0.690, P = 0.038, respectively), while MMP9 gene expression with Necrotic Core PV (Coefficient 70.559, SE 32.629, P = 0.034), independently from traditional cardiovascular risk factors, medications, and presence of obstructive CAD. After transcriptomic analysis, MMP9 expression was linked to expression of genes involved in the innate immunity.
Among CCS patients, MMP9 is an independent predictive marker of progression of adverse coronary plaques, possibly reflecting the activity of inflammatory pathways conditioning adverse plaque phenotypes. Thus, blood MMP9 might be used for the identification of patients with residual risk even with optimal management of classical cardiovascular risk factors who may derive the greatest benefit from targeted anti-inflammatory drugs.
MMP-9 是动脉粥样硬化斑块不稳定和不良心血管事件的预测因子，但缺乏 MMP9 与冠状动脉疾病进展之间的纵向数据。本研究旨在探讨 MMP9 是否与稳定型慢性冠状动脉综合征（CCS）患者的动脉粥样硬化斑块进展相关，以及相关的分子基础。
在基线时和随访 6.5±1.1 年后，对 157 例接受冠状动脉计算机断层扫描血管造影的 CCS 患者（58±8 岁；66%为男性）测量 MMP9 血清水平，以评估总斑块体积（PV）、纤维斑块 PV、纤维脂肪斑块 PV、坏死核心 PV 和致密钙斑块 PV 的进展。通过 RNA-seq 进行转录组分析，评估全血中的基因表达。
在多变量分析中，血清 MMP9 与总斑块和坏死核心 PV 的年度变化相关（系数分别为 3.205，SE 为 1.321，P=0.017；1.449，SE 为 0.690，P=0.038），而 MMP9 基因表达与坏死核心 PV 相关（系数为 70.559，SE 为 32.629，P=0.034），独立于传统心血管危险因素、药物和阻塞性 CAD 的存在。经过转录组分析，MMP9 的表达与参与固有免疫的基因的表达相关。
在 CCS 患者中，MMP9 是不良冠状动脉斑块进展的独立预测标志物，可能反映了调节不良斑块表型的炎症途径的活性。因此，即使在对经典心血管危险因素进行最佳管理的情况下，血液 MMP9 也可用于识别残余风险的患者，这些患者可能从靶向抗炎药物中获益最大。
