Phenotypic characterization of primary cardiac fibroblasts from patients with HFpEF.
Phenotypic characterization of primary cardiac fibroblasts from patients with HFpEF.
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DOI：
10.1371/journal.pone.0262479
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Bradshaw AD
中科院分区：
文献类型：
--
作者：
Zhang Y;Van Laer AO;Baicu CF;Neff LS;Hoffman S;Katz MR;Zeigler SM;Zile MR;Bradshaw AD
心力衰竭是全球住院和死亡的主要原因。射血分数保留性心力衰竭（HFpEF）是一项重大的临床挑战，因为诊断为HFpEF的患者缺乏可用的治疗方式。HFpEF的一个症状是与左心室僵硬度增加相关的舒张功能受损。心肌纤维胶原含量的增加是导致心肌硬度增加的一个因素。心脏成纤维细胞是在心脏中产生纤维状胶原的主要细胞类型。然而，对HFpEF心肌中心脏成纤维细胞的表型变化知之甚少。在本研究中，从接受心血管介入治疗的患者的左心室心外膜活检中建立心脏成纤维细胞，并分为三类：参考对照、无心力衰竭的高血压（HTN（-）HFpEF）和高血压伴心力衰竭（HTN（+）HFpEF）。活检评价心肌细胞横截面积（CSA）和胶原体积分数。评估原代成纤维细胞培养物的增殖和I型胶原蛋白、膜1型基质金属蛋白酶（MT 1-MMP）和α平滑肌肌动蛋白（αSMA）蛋白表达的差异。HTN（-）HFpEF和HTN（+）HFpEF的活检显示肌细胞CSA比对照组增加，尽管只有HTN（+）HFpEF显示纤维胶原含量显著增加。与参考对照相比，在HTN（-）HFpEF或HTN（+）HFpEF培养物中未检测到增殖或αSMA的显著变化。在HF（-）HFpEF成纤维细胞中检测到I型胶原蛋白的产生显著增加，而在HTN（+）HFpEF细胞中检测到MT 1-MMP水平显著降低。我们得出结论，心外膜活检为原代成纤维细胞培养物提供了一个可行的来源，HTN（-）HFpEF和HTN（+）HFpEF细胞与参考对照相比，证明了表型差异。
Heart failure is a leading cause of hospitalizations and mortality worldwide. Heart failure with a preserved ejection fraction (HFpEF) represents a significant clinical challenge due to the lack of available treatment modalities for patients diagnosed with HFpEF. One symptom of HFpEF is impaired diastolic function that is associated with increases in left ventricular stiffness. Increases in myocardial fibrillar collagen content is one factor contributing to increases in myocardial stiffness. Cardiac fibroblasts are the primary cell type that produce fibrillar collagen in the heart. However, relatively little is known regarding phenotypic changes in cardiac fibroblasts in HFpEF myocardium. In the current study, cardiac fibroblasts were established from left ventricular epicardial biopsies obtained from patients undergoing cardiovascular interventions and divided into three categories: Referent control, hypertension without a heart failure designation (HTN (-) HFpEF), and hypertension with heart failure (HTN (+) HFpEF). Biopsies were evaluated for cardiac myocyte cross-sectional area (CSA) and collagen volume fraction. Primary fibroblast cultures were assessed for differences in proliferation and protein expression of collagen I, Membrane Type 1-Matrix Metalloproteinase (MT1-MMP), and α smooth muscle actin (αSMA). Biopsies from HTN (-) HFpEF and HTN (+) HFpEF exhibited increases in myocyte CSA over referent control although only HTN (+) HFpEF exhibited significant increases in fibrillar collagen content. No significant changes in proliferation or αSMA was detected in HTN (-) HFpEF or HTN (+) HFpEF cultures versus referent control. Significant increases in production of collagen I was detected in HF (-) HFpEF fibroblasts, whereas significant decreases in MT1-MMP levels were measured in HTN (+) HFpEF cells. We conclude that epicardial biopsies provide a viable source for primary fibroblast cultures and that phenotypic differences are demonstrated by HTN (-) HFpEF and HTN (+) HFpEF cells versus referent control.
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影响因子：
64.8
作者：
Litviňuková M;Talavera-López C;Maatz H;Reichart D;Worth CL;Lindberg EL;Kanda M;Polanski K;Heinig M;Lee M;Nadelmann ER;Roberts K;Tuck L;Fasouli ES;DeLaughter DM;McDonough B;Wakimoto H;Gorham JM;Samari S;Mahbubani KT;Saeb-Parsy K;Patone G;Boyle JJ;Zhang H;Zhang H;Viveiros A;Oudit GY;Bayraktar OA;Seidman JG;Seidman CE;Noseda M;Hubner N;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
37.8
作者：
Bradshaw AD;Baicu CF;Rentz TJ;Van Laer AO;Boggs J;Lacy JM;Zile MR
通讯作者：
Zile MR
影响因子：
24
作者：
Nagaraju, Chandan K.;Robinson, Emma L.;Sipido, Karin R.
通讯作者：
Sipido, Karin R.
影响因子：
158.5
作者：
Zile, MR;Baicu, CF;Gaasch, WH
通讯作者：
Gaasch, WH
DOI：
10.1152/ajpheart.00552.2020
发表时间：
2021-02-01
影响因子：
4.8
作者：
Riley, Hannah J.;Kelly, Ryan R.;Bradshaw, Amy D.
通讯作者：
Bradshaw, Amy D.