Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
Division of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
PLoS One. 2022 Jan 11;17(1):e0262479. doi: 10.1371/journal.pone.0262479. eCollection 2022.
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.
心力衰竭是全球范围内导致住院和死亡的主要原因。射血分数保留的心力衰竭（HFpEF）代表了一个重大的临床挑战，因为对于被诊断为 HFpEF 的患者，缺乏可用的治疗方法。HFpEF 的一个症状是舒张功能障碍，这与左心室僵硬度增加有关。心肌原纤维胶原含量的增加是导致心肌僵硬度增加的一个因素。心脏成纤维细胞是心脏中产生原纤维胶原的主要细胞类型。然而，对于 HFpEF 心肌中成纤维细胞的表型变化，相对知之甚少。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了心脏成纤维细胞，并分为三类：参照对照、无心力衰竭指定的高血压（HTN（-）HFpEF）和心力衰竭合并高血压（HTN（+）HFpEF）。评估活检的心肌细胞横截面积（CSA）和胶原体积分数。对原代成纤维细胞培养物进行增殖和胶原 I、膜型 1-基质金属蛋白酶（MT1-MMP）和α平滑肌肌动蛋白（αSMA）蛋白表达的差异进行评估。HTN（-）HFpEF 和 HTN（+）HFpEF 的活检显示心肌细胞 CSA 较参照对照增加，尽管仅 HTN（+）HFpEF 显示原纤维胶原含量显著增加。在 HTN（-）HFpEF 或 HTN（+）HFpEF 培养物与参照对照相比，未检测到增殖或αSMA 的显著变化。HF（-）HFpEF 成纤维细胞中胶原 I 的产生显著增加，而 HTN（+）HFpEF 细胞中 MT1-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提供了可行的来源，HTN（-）HFpEF 和 HTN（+）HFpEF 细胞与参照对照相比表现出表型差异。
