Sedgwick Bryony, Riches Kirsten, Bageghni Sumia A, O'Regan David J, Porter Karen E, Turner Neil A
Division of Cardiovascular and Diabetes Research, School of Medicine, University of Leeds, Leeds, UK.
Division of Cardiovascular and Diabetes Research, School of Medicine, University of Leeds, Leeds, UK; Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK.
Cardiovasc Pathol. 2014 Jul-Aug;23(4):204-10. doi: 10.1016/j.carpath.2014.03.004. Epub 2014 Mar 26.
Type 2 diabetes mellitus (T2DM) promotes adverse myocardial remodeling and increased risk of heart failure; effects that can occur independently of hypertension or coronary artery disease. As cardiac fibroblasts (CFs) are key effectors of myocardial remodeling, we investigated whether inherent phenotypic differences exist in CF derived from T2DM donors compared with cells from nondiabetic (ND) donors.
Cell morphology (cell area), proliferation (cell counting over 7-day period), insulin signaling [phospho-Akt and phospho-extracellular signal-regulated kinase (ERK) Western blotting], and mRNA expression of key remodeling genes [real-time reverse transcription-polymerase chain reaction (RT-PCR)] were compared in CF cultured from atrial tissue from 14 ND and 12 T2DM donors undergoing elective coronary artery bypass surgery.
The major finding was that Type I collagen (COL1A1) mRNA levels were significantly elevated by twofold in cells derived from T2DM donors compared with those from ND donors; changes reflected at the protein level. T2DM cells had similar proliferation rates but a greater variation in cell size and a trend towards increased cell area compared with ND cells. Insulin-induced Akt and ERK phosphorylation were similar in the two cohorts of cells.
CF from T2DM individuals possess an inherent profibrotic phenotype that may help to explain the augmented cardiac fibrosis observed in diabetic patients.
We investigated whether inherent phenotypic differences exist between CF cultured from donors with or without Type 2 diabetes. Cell morphology, proliferation, insulin signaling, and gene expression were compared between multiple cell populations. The major finding was that Type I collagen levels were elevated in fibroblasts from diabetic donors, which may help explain the augmented cardiac fibrosis observed with diabetes.
2型糖尿病（T2DM）会促进不良心肌重塑并增加心力衰竭风险；这些影响可能独立于高血压或冠状动脉疾病而发生。由于心脏成纤维细胞（CFs）是心肌重塑的关键效应细胞，我们研究了与非糖尿病（ND）供体来源的细胞相比，T2DM供体来源的CFs是否存在内在表型差异。
对14名ND和12名接受择期冠状动脉搭桥手术的T2DM供体心房组织培养的CFs，比较其细胞形态（细胞面积）、增殖（7天内细胞计数）、胰岛素信号传导[磷酸化Akt和磷酸化细胞外信号调节激酶（ERK）的蛋白质印迹法]以及关键重塑基因的mRNA表达[实时逆转录-聚合酶链反应（RT-PCR）]。
主要发现是，与ND供体来源的细胞相比，T2DM供体来源的细胞中I型胶原（COL1A1）mRNA水平显著升高两倍；这种变化在蛋白质水平也有体现。T2DM细胞的增殖率相似，但与ND细胞相比，细胞大小变化更大且有细胞面积增加的趋势。两组细胞中胰岛素诱导的Akt和ERK磷酸化相似。
T2DM个体的CFs具有内在的促纤维化表型，这可能有助于解释糖尿病患者中观察到的心脏纤维化加剧现象。
我们研究了2型糖尿病患者和非糖尿病患者来源的CFs之间是否存在内在表型差异。比较了多个细胞群体的细胞形态、增殖、胰岛素信号传导和基因表达。主要发现是糖尿病供体来源成纤维细胞中的I型胶原水平升高，这可能有助于解释糖尿病患者中观察到的心脏纤维化加剧现象。
