Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, USA.
Am J Physiol Heart Circ Physiol. 2012 Nov 1;303(9):H1128-34. doi: 10.1152/ajpheart.00482.2012. Epub 2012 Aug 31.
Myocardial fibrillar collagen is considered an important determinant of increased ventricular stiffness in pressure-overload (PO)-induced cardiac hypertrophy. Chronic PO was created in feline right ventricles (RV) by pulmonary artery banding (PAB) to define the time course of changes in fibrillar collagen content after PO using a nonrodent model and to determine whether this time course was dependent on changes in fibroblast function. Total, soluble, and insoluble collagen (hydroxyproline), collagen volume fraction (CVF), and RV end-diastolic pressure were assessed 2 days and 1, 2, 4, and 10 wk following PAB. Fibroblast function was assessed by quantitating the product of postsynthetic processing, insoluble collagen, and levels of SPARC (secreted protein acidic and rich in cysteine), a protein that affects procollagen processing. RV hypertrophic growth was complete 2 wk after PAB. Changes in RV collagen content did not follow the same time course. Two weeks after PAB, there were elevations in total collagen (control RV: 8.84 ± 1.03 mg/g vs. 2-wk PAB: 11.50 ± 0.78 mg/g); however, increased insoluble fibrillar collagen, as measured by CVF, was not detected until 4 wk after PAB (control RV CVF: 1.39 ± 0.25% vs. 4-wk PAB: 4.18 ± 0.87%). RV end-diastolic pressure was unchanged at 2 wk, but increased until 4 wk after PAB. RV fibroblasts isolated after 2-wk PAB had no changes in either insoluble collagen or SPARC expression; however, increases in insoluble collagen and in levels of SPARC were detected in RV fibroblasts from 4-wk PAB. Therefore, the time course of PO-induced RV hypertrophy differs significantly from myocardial fibrosis and diastolic dysfunction. These temporal differences appear dependent on changes in fibroblast function.
心肌原纤维胶原被认为是压力超负荷（PO）诱导的心脏肥厚中心室僵硬度增加的重要决定因素。通过肺动脉结扎（PAB）在猫右心室（RV）中创建慢性 PO，以使用非啮齿动物模型定义 PO 后纤维胶原含量变化的时间过程，并确定该时间过程是否依赖于成纤维细胞功能的变化。在 PAB 后 2 天和 1、2、4 和 10 周时评估总胶原、可溶性胶原和不溶性胶原（羟脯氨酸）、胶原体积分数（CVF）和 RV 舒张末期压。通过定量测定后合成加工产物、不溶性胶原和富含半胱氨酸酸性分泌蛋白（SPARC）的水平来评估成纤维细胞功能，SPARC 是一种影响前胶原加工的蛋白质。PAB 后 2 周 RV 发生完全肥大。RV 胶原含量的变化没有遵循相同的时间过程。PAB 后 2 周，总胶原增加（对照 RV：8.84±1.03mg/g 比 2 周 PAB：11.50±0.78mg/g）；然而，直到 PAB 后 4 周才检测到 CVF 增加的不溶性纤维状胶原（对照 RV CVF：1.39±0.25%比 4 周 PAB：4.18±0.87%）。PAB 后 2 周 RV 舒张末期压不变，但直到 4 周后才增加。PAB 后 2 周分离的 RV 成纤维细胞在不溶性胶原或 SPARC 表达方面没有变化；然而，在 4 周 PAB 的 RV 成纤维细胞中检测到不溶性胶原和 SPARC 水平增加。因此，PO 诱导的 RV 肥大的时间过程与心肌纤维化和舒张功能障碍显著不同。这些时间差异似乎依赖于成纤维细胞功能的变化。
