Studies on apoptosis and fibrosis in skeletal musculature: a comparison of heart failure patients with and without cardiac cachexia
Studies on apoptosis and fibrosis in skeletal musculature: a comparison of heart failure patients with and without cardiac cachexia
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DOI：
10.1016/s0167-5273(02)00535-1
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发表时间：
2003-07-01
影响因子：
3.5
通讯作者：
Uhal, B
中科院分区：
文献类型：
--
作者：
Filippatos, GS;Kanatselos, C;Uhal, B
在慢性心力衰竭（CHF）患者的骨骼肌中发现细胞凋亡，并且与运动不耐受有关。在CHF中，恶病质的特征是神经激素激活和肌肉萎缩。神经激素激活可导致细胞死亡和纤维化。该研究的目的是确定患有CHF和恶病质的患者骨骼肌细胞凋亡和纤维化的严重程度及其与这些患者运动不耐受的关系。通过原位末端标记 (ISEL) 检测细胞凋亡和 Picrosirius Red 技术检测胶原蛋白，对 21 名 CHF 患者（8 名恶病质）和 4 名年龄相仿的健康对照者的骨骼肌活检进行了研究。 ISEL 在 52% 的 CHF 患者（21 名中的 11 名）中检测到骨骼肌细胞凋亡，而对照组则没有检测到。骨骼肌细胞凋亡阳性的 CHF 患者运动耐量受损（峰值耗氧量 11.4 +/- 5.7 vs. 16.91 +/- 6.6，P=0.029）。 Picrosirius Red 在 21 名 CHF 患者中检测到 8 名胶原蛋白增加，而对照组则没有检测到。 8 名恶病质患者中的 6 名检测到胶原蛋白增加（纤维化），13 名无恶病质患者中的 2 名检测到胶原蛋白增加（纤维化）（P = 0.01）。恶病质和非恶病质患者的峰值耗氧量和细胞凋亡相似。因此，心脏恶病质患者的骨骼肌组织的特征是存在纤维化。未发现恶病质 CHF 患者中细胞凋亡更为频繁。我们的数据支持这样的假设：恶病质通过不同的机制导致CHF患者的骨骼肌肌病，并且不同的机制与运动耐量恶化和心脏恶病质的进展有关。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Apoptosis has been found in skeletal muscles of patients with chronic heart failure (CHF) and has been associated with exercise intolerance. In CHF, cachexia is characterized by neurohormonal activation and muscle wasting. Neurohormonal activation can lead to cell death and fibrosis. The purpose of the study was to determine the severity of apoptosis and fibrosis in skeletal muscles of patients with CHF and cachexia and its relationship to exercise intolerance in these patients. Skeletal muscle biopsies of 21 patients with CHF (eight with cachexia) and four healthy controls of similar age have been studied by in situ end labeling (ISEL) for apoptosis and by the Picrosirius Red technique for collagen. Apoptosis in skeletal muscles was detected by ISEL in 52% of the patients with CHF (11 out of 21) and in none of the controls. CHF patients with apoptosis-positive skeletal muscles had impaired exercise tolerance (peak oxygen consumption 11.4 +/- 5.7 vs. 16.91 +/- 6.6, P=0.029). Increased collagen was detected by Picrosirius Red in eight out of 21 patients with CHF and in none of the controls. Increased collagen (fibrosis) was detected in six out of eight patients with cachexia and in two out of 13 patients without cachexia (P=0.01). Peak oxygen consumption and apoptosis were similar in cachectic and non-cachectic patients. Thus, the skeletal musculature of patients with cardiac cachexia is characterised by the presence of fibrosis. Apoptosis was not found to be more frequent in cachectic CHF patients. Our data support the hypothesis that cachexia contributes by a different mechanism to skeletal muscle myopathy of CHF patients and different mechanisms are implicated in deterioration of exercise tolerance and progression to cardiac cachexia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.