Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure Potential Role of Lysyl Oxidase
Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure Potential Role of Lysyl Oxidase
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DOI：
10.1161/hypertensionaha.112.196113
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发表时间：
2012-09-01
期刊：
影响因子：
8.3
通讯作者：
Diez, Javier
中科院分区：
文献类型：
--
作者：
Lopez, Begona;Querejeta, Ramon;Diez, Javier
我们研究了38例高血压合并慢性心力衰竭C期患者的心肌胶原质量是否与左侧充盈压升高相关。充盈压通过有创测量肺毛细血管楔压进行评估。根据二尖瓣充盈波早期的减速时间计算左心室腔室刚度常数。组织形态学评价心肌总胶原组织和I型胶原纤维所占的心肌体积分数。胶原蛋白交联度（CCL）决定了不溶性硬胶原蛋白的形成，通过比色和酶法评估。通过Western blot评估调节CCL的赖氨酰氧化酶（LOX）的表达。与正常肺毛细血管楔压（12 mm Hg; n = 22）的患者相比，表现出增加的左心室腔室刚度常数，心肌体积的分数所占的总胶原组织，心肌体积的分数所占的I型胶原纤维，CCL，不溶性硬胶原，和LOX。肺毛细血管楔压与左室腔僵硬度常数相关（r = 0.639; P < 0.001），不溶性硬胶原（r = 0.474; P < 0.005），CCL（r = 0.625; P < 0.001），LOX（r = 0.410; P < 0.05），但与对照组比较，差异无显著性（P> 0.05）。所有患者中，但不具有总胶原组织占据的心肌体积分数或胶原类型占据的心肌体积分数我纤维。此外，CCL与不溶性硬胶原相关（r = 0.612; P < 0.005），LOX（r = 0.538; P < 0.01），左室腔僵硬度常数（r = 0.535; P < 0.005），峰值充盈率射血分数（r =-0.343，P < 0.05）脑钠肽氨基末端前肽（r = 0.421; P < 0.05）。这些关联独立于混杂因素。这些发现表明，在C期心力衰竭的高血压患者中，只有胶原的质量（即交联程度）与充盈压升高相关。这表明，LOX介导的过度CCL促进左心室僵硬度的增加，从而导致这些患者的充盈压升高。（高血压。2012; 60：677-683）。.在线补充资料
We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (12 mm Hg; n = 22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (r = 0.639; P < 0.001), insoluble stiff collagen (r = 0.474; P < 0.005), CCL (r = 0.625; P < 0.001), and LOX (r = 0.410; P < 0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (r = 0.612; P < 0.005), LOX (r = 0.538; P < 0.01), left ventricular chamber stiffness constant (r = 0.535; P < 0.005), peak filling rate (r =- 0.343; P < 0.05), ejection fraction (r =- 0.430; P < 0.01), and amino-terminal propeptide of brain natriuretic peptide (r = 0.421; P < 0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients. (Hypertension. 2012; 60: 677-683.) . Online Data Supplement