Martos Ramón, Baugh John, Ledwidge Mark, O'Loughlin Christina, Conlon Carmel, Patle Anil, Donnelly Seamas C, McDonald Kenneth
Heart Failure Unit, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Circulation. 2007 Feb 20;115(7):888-95. doi: 10.1161/CIRCULATIONAHA.106.638569. Epub 2007 Feb 5.
The pathophysiology of diastolic heart failure (DHF) is poorly understood. One potential explanation is an active fibrotic process that produces increased ventricular stiffness, which compromises filling. The present study investigates collagen metabolism in hypertensive patients in different phases of diastolic function with and without proven DHF.
We studied 86 hypertensive patients divided into groups according to the presence of DHF (32 with, 54 without) and phase of diastolic function (20 with normal function, 38 with impaired relaxation, 10 with pseudonormalization, and 16 with restrictive-like filling). Serum carboxy-terminal, amino-terminal, and carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, matrix metalloproteinases (MMPs; total MMP-1, active MMP-2, and MMP-9), and tissue inhibitor of MMPs levels were assayed by radioimmunoassay and ELISA. Doppler-echocardiographic assessment of diastolic filling was made with measurements of E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Serum carboxy-terminal telopeptide of procollagen type I, carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 levels (P<0.001 for all, controlled for age and gender) were greater in patients with DHF than in those without. When we controlled for age and gender, levels of serum carboxy-terminal telopeptide of procollagen type I, tissue inhibitor of MMP-1, amino-terminal propeptide of procollagen type III (all P<0.001), carboxy-terminal telopeptide of procollagen type I (P=0.008), and MMP-2 (P=0.03) were greater in more severe phases of diastolic dysfunction. Within phases of diastolic dysfunction, serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 were elevated in those with DHF compared with those without DHF (all P<0.001).
These data demonstrate serological evidence of an active fibrotic process in DHF, which is more marked in more severe diastolic dysfunction. This observation may help explain the pathophysiology of DHF and may suggest new avenues for diagnostic and therapeutic intervention.
舒张性心力衰竭（DHF）的病理生理学尚未完全明确。一种可能的解释是存在活跃的纤维化过程，导致心室僵硬度增加，进而影响心室充盈。本研究调查了不同舒张功能阶段、有无确诊DHF的高血压患者的胶原代谢情况。
我们研究了86例高血压患者，根据是否存在DHF（32例有，54例无）以及舒张功能阶段（20例功能正常，38例舒张功能受损，10例呈假性正常化，16例呈限制性充盈样）进行分组。采用放射免疫分析和酶联免疫吸附测定法检测血清I型前胶原羧基末端、氨基末端及羧基末端肽、III型前胶原氨基末端前肽、基质金属蛋白酶（MMPs；总MMP-1、活性MMP-2和MMP-9）以及MMPs组织抑制剂水平。通过测量E/A比值、E波减速时间和等容舒张时间进行多普勒超声心动图舒张期充盈评估。DHF患者的血清I型前胶原羧基末端肽、I型前胶原羧基末端肽、III型前胶原氨基末端前肽、MMP-2和MMP-9水平（校正年龄和性别后，所有P<0.001）高于无DHF患者。校正年龄和性别后，舒张功能障碍更严重阶段的血清I型前胶原羧基末端肽、MMP-1组织抑制剂、III型前胶原氨基末端前肽（均P<0.001）、I型前胶原羧基末端肽（P=0.008）和MMP-2（P=0.03）水平更高。在舒张功能障碍各阶段中，与无DHF患者相比，有DHF患者的血清I型前胶原羧基末端肽、III型前胶原氨基末端前肽、MMP-2和MMP-9水平均升高（所有P<0.001）。
这些数据证明了DHF中存在活跃纤维化过程的血清学证据，在更严重的舒张功能障碍中更为明显。这一观察结果可能有助于解释DHF的病理生理学，并可能为诊断和治疗干预提供新途径。
