Protein concentration and mitochondrial content in the gastrocnemius predicts mortality rates in patients with peripheral arterial disease.
Protein concentration and mitochondrial content in the gastrocnemius predicts mortality rates in patients with peripheral arterial disease.
复制标题
腓肠肌中的蛋白质浓度和线粒体含量可预测外周动脉疾病患者的死亡率。
DOI：
10.1097/sla.0000000000000643
复制
发表时间：
2015
影响因子：
9
通讯作者：
Pipinos,II
中科院分区：
文献类型：
--
作者：
Thompson,JR;Swanson,SA;Haynatzki,G;Koutakis,P;Johanning,JM;Reppert,PR;Papoutsi,E;Miserlis,D;Zhu,Z;Casale,GP;Pipinos,II
目的：本研究评估外周动脉疾病（PAD）患者腓肠肌活检中蛋白质浓度和线粒体含量预测死亡率的假设。背景：PAD患者经历以线粒体功能障碍、肌纤维降解和缺血性腿部纤维化为特征的进展性肌病，沿着死亡率增加。将蛋白质浓度归一化为肌肉湿重，并将柠檬酸合酶活性（细胞中线粒体含量的标准量度）归一化为肌肉湿重和蛋白质浓度。将蛋白质和柠檬酸合酶数据分组为三分位数，用Kaplan-Meier曲线确定每个三分位数的5年全因死亡率，并通过改良的Peto-Peto检验进行比较。Cox回归模型为每个变量控制的临床feature.Results的影响：在187名研究参与者，46人死亡，平均随访23.0个月。蛋白质浓度最低三分位数的患者的五年死亡率最高。柠檬酸合酶活性在中间三分位的患者死亡率最低，当标准化为肌肉湿重或蛋白质浓度时。考克斯分析的死亡率风险比（HR）对于标准化为肌肉湿重的蛋白质浓度具有统计学显著性（最低与中间三分位数; HR= 2.93; P= 0.008）和柠檬酸合酶标准化为蛋白质浓度（最低与中间三分位数; HR= 4.68; P= 0.003;以及最低与最高三分位数; HR= 2.36; P= 0.027）。结论：PAD患者的同期人群的存活分析鉴定了他们腓肠肌的蛋白质和线粒体含量作为死亡率的预测因子。
Objective:This study evaluated the hypothesis that protein concentration and mitochondrial content in gastrocnemius biopsies from patients with peripheral arterial disease (PAD) predict mortality rates.Background:PAD patients experience advancing myopathy characterized by mitochondrial dysfunction, myofiber degradation, and fibrosis in their ischemic legs, along with increased mortality rates.Methods:Samples from the gastrocnemius of PAD patients were used for all analyses. Protein concentration was normalized to muscle wet weight, and citrate synthase activity (standard measure of mitochondrial content in cells) was normalized to muscle wet weight and protein concentration. Protein and citrate synthase data were grouped into tertiles and 5-year, all-cause mortality for each tertile was determined with Kaplan-Meier curves and compared by the modified Peto-Peto test. A Cox-regression model for each variable controlled for the effects of clinical characteristics.Results:Of the 187 study participants, 46 died during a mean follow-up of 23.0 months. Five-year mortality rate was highest for patients in the lowest tertile of protein concentration. Mortality was lowest for patients in the middle tertile of citrate synthase activity when normalized to either muscle wet weight or protein concentration. The mortality hazard ratios (HRs) from the Cox analysis were statistically significant for protein concentration normalized to muscle wet weight (lowest vs middle tertile; HR= 2.93; P= 0.008) and citrate synthase normalized to protein concentration (lowest vs middle tertile; HR= 4.68; P= 0.003; and lowest vs highest tertile; HR= 2.36; P= 0.027).Conclusions:Survival analysis of a contemporaneous population of PAD patients identifies protein and mitochondrial content of their gastrocnemius as predictors of mortality rate.