Regional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction.
Regional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction.
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DOI：
10.1016/j.hrthm.2022.01.022
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发表时间：
2022-05
期刊：
影响因子：
5.5
通讯作者：
Spinale, Francis G.
中科院分区：
文献类型：
--
作者：
Stacy, Mitchel R.;Lin, Ben A.;Thorn, Stephanie L.;Lobb, David C.;Max, Mark W.;Novack, Craig;Zellars, Kia N.;Freeburg, Lisa;Akar, Joseph G.;Sinusas, Albert J.;Spinale, Francis G.
关键词：
心肌梗死(MI)后左室(LV)重构与新发的房颤(AF)相关。心肌梗死后左室重构以基质金属蛋白酶(MMPs)及其组织抑制物(TIMPs)的局部变化为特征，导致细胞外基质(ECM)重构。本研究验证了心肌梗死后局部心房基质金属蛋白酶活性、基质金属蛋白酶/TIMP表达和细胞外基质重塑发生改变的假说，从而增加了房颤的易感性。心肌梗死猪(25 kg；冠脉结扎；n=9)诱导心肌梗死，在心肌梗死后约14天，进行心房电刺激。然后，注入一种基质金属蛋白酶放射性示踪剂，进行基质金属蛋白酶/组织金属蛋白酶组织化学分析和细胞外基质胶原的组织化学检测。另设7头非心肌梗死猪作为对照。心肌梗死后89%(8/9)的猪可诱发房颤，而对照组均未发生房颤。心肌梗死后，大多数心房区域的基质金属蛋白酶活性(基质金属蛋白酶放射性示踪剂摄取)增加约2倍，而右心房区域的纤维胶原含量不变或实际上减少，而左心房区域的胶原含量增加。MMPTIMP图谱显示从左心耳到右心房区呈不均匀分布。心梗后早期房颤易损性与心房ECM重塑的异质性模式有关，可通过无创分子成像检测到。检测心梗后早期心房基质金属蛋白酶的激活可能有助于确定房颤背后的心肌基质。
Left ventricular (LV) remodeling following a myocardial infarction (MI) is associated with new onset atrial fibrillation (AF). LV remodeling post-MI is characterized by regional changes in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), causing extracellular matrix (ECM) remodeling. This study tested the hypothesis that a shift in regional atrial MMP activity, MMP/TIMP expression, and ECM remodeling occurs post-MI, which cause increased vulnerability to AF. MI was induced in pigs (25 kg; coronary ligation; n=9), and at approximately 14 days post-MI, an atrial electrical stimulation protocol was performed. Following which, an MMP radiotracer was infused, MMP/TIMP mRNA profiling performed, and ECM collagen assessed by histochemistry. An additional 7 non-MI pigs served as controls. AF could be induced in 89% (8/9) of the post-MI pigs but none of the controls. MMP activity (MMP radiotracer uptake) increased by approximately 2-fold in most atrial regions post-MI, whereas fibrillar collagen content was unchanged or actually reduced in right atrial regions and increased in left atrial regions. MMP/TIMP profiles revealed a heterogeneous pattern from the left atrial appendage to right atrial regions. AF vulnerability early post-MI was associated with a heterogeneous pattern of atrial ECM remodeling, detectable by non-invasive molecular imaging. Detection of early atrial MMP activation post-MI may help define the myocardial substrate underlying AF.
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