Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy
Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy
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DOI：
10.1016/j.ahj.2008.01.035
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发表时间：
2008-07-01
影响因子：
4.8
通讯作者：
Vicente, Vicente
中科院分区：
文献类型：
--
作者：
Roldan, Vanessa;Marin, Francisco;Vicente, Vicente
背景肥厚型心肌病（HCM）的定义是存在原因不明的左心室肥大、心肌细胞紊乱和间质纤维化。细胞外基质的增加通过增加I/III型胶原蛋白的量而产生间质纤维化。心脏磁共振（CMR）显示心肌晚期钆增强的区域代表心肌胶原增加。关于基质金属蛋白酶（MMPs）在心肌重塑和随后的纤维化中的作用，本研究的目的是探讨MMP系统与CMR心肌晚期增强的关系（作为图像记录的纤维化的表达）和N-末端脑钠肽前体（NT-proBNP）（作为心脏超负荷的标志物）在HCM.Methods我们包括67例HCM患者（44名男性，年龄49 - 14岁），并与58名年龄和性别相似的对照组进行了比较。记录猝死的危险因素。使用钆进行盲态CMR。采用酶联免疫吸附法测定血浆基质金属蛋白酶1、MMP-2和MMP-9水平。结果50%以上的患者血清MMP-1水平低于该技术的最低检测限。HCM患者MMP-2、MMP-9和NT-proBNP水平升高（均P <0.01）。基质金属蛋白酶2与呼吸困难相关（P = 0.049），与MMP-9（r = 0.28，P = 0.025）和NT-proBNP（r = 0.39，P = 0.001）相关。基质金属蛋白酶9与CMR中钆增强的存在相关（P = .001），与NT-proBNP相关（r = 0.52，P < .001）。NT-proBNP也与钆增强相关（P = .006）。MMP-2和MMP-9与运动能力（代谢当量单位）呈负相关（r分别为-0.36和-0.42，均P <0.01）。在多变量分析（调整猝死危险因素和超声心动图标记），只有MMP-9与纤维化（P = 0.011）。结论基质金属蛋白酶9是独立相关的钆增强CMR肥厚型心肌病患者，这表明MMP系统在心脏重塑和纤维化在这种情况下有重要作用。
Background Hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, myocyte disarray, and interstitial fibrosis. An increase in extracellular matrix produces interstitial fibrosis, by raised amounts of collagen type I/III. Regions of myocardial late gadolinium enhancement by cardiac magnetic resonance (CMR) represented increased myocardial collagen. Regarding the role of matrix metalloproteinases (MMPs) in myocardial remodeling and subsequent fibrosis, the aim of our study was to explore the relation between MMP system and myocardial late gadolinium enhancement by CMR (as expression of image-documented fibrosis) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (as a marker of cardiac overload) in HCM.Methods We included 67 HCM patients (44 men aged 49 14 years) and were compared to 58 controls with similar age and sex. Risk factors for sudden death were recorded. A blinded CMR was performed with gadolinium. Matrix metalloproteinase 1, MMP-2, and MMP-9 plasma levels were assayed by enzyme-linked immunosorbent assay. Serum samples were used for measurement of NT-proBNP.Results In patients, >50% of MMP-1 values were below the lowest limit of detection of the technique. Raised levels of MMP-2, MMP-9, and NT-proBNP were observed in HCM patients (all P < .01). Matrix metalloproteinase 2 was associated with dyspnea (P = .049) and correlated with MMP-9 (r = 0.28, P =.025) and NT-proBNP (r = 0.39, P = .001). Matrix metalloproteinase 9 was associated with the presence of gadolinium enhancement in CMR (P = .001) and correlated with NT-proBNP (r = 0.52, P < .001). NT-proBNP was also associated with gadolinium enhancement (P = .006). Both MMP-2 and MMP-9 correlated negatively with exercise capacity (metabolic equivalent units), (r = -0.36 and r = -0.42 respectively, both P < .01). On multivariate analysis (adjusted by sudden death risk factors and echocardiographic markers), only MMP-9 was associated with fibrosis (P = .011).Conclusions Matrix metalloproteinase 9 is independently associated with gadolinium enhancement on CMR in patients with hypertrophic cardiomyopathy, suggesting that the MMP system has an important role in cardiac remodeling and fibrosis in this condition.