Elevated circulating fibrocyte levels in patients with hypertensive heart disease.

Elevated circulating fibrocyte levels in patients with hypertensive heart disease.
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DOI:
10.1097/hjh.0b013e32835639bb
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发表时间:
2012-09
影响因子:
4.9
通讯作者:
Kramer CM
Kramer CM
中科院分区:
医学2区
文献类型:
--
作者:
Keeley EC;Mehrad B;Janardhanan R;Salerno M;Hunter JR;Burdick MM;Field JJ;Strieter RM;Kramer CM

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尸检和活组织检查研究表明,与正常心脏相比,高血压心脏病患者的心脏纤维化明显增加。纤维细胞是一种循环的骨髓源性细胞,已被证明可以在多种疾病中归巢组织并促进瘢痕形成,但迄今为止尚未研究其在人类高血压心脏病中的作用。我们的目标是确定高血压心脏病患者的纤维细胞水平是否升高。我们测量了12例高血压性心脏病患者的外周血纤维细胞水平及其活化表型,这些患者通过无创成像左心室质量增加来确定,并将其与19例健康正常对照的纤维细胞水平进行了比较,并将其与心脏MRI结果相关联。与正常对照组相比,高血压性心脏病患者的循环中总纤维细胞水平显著升高[中位数(四分位距); 149000(62200-220000)与564500(321000-1.2900e+006),P < 0.0001]以及活化的纤维细胞[15700(6380-19800)vs. 478500(116500-1.2360e+006)P < 0.0001]。高血压性心脏病患者表达趋化因子CXCR 4(P < 0.0001)、CCR 2(P < 0.0001)、CCR 7(P < 0.0001)及CXCR 4和CCR 2共表达(P < 0.0001)的纤维细胞亚群明显高于对照组。高血压性心脏病患者左室重量指数与总纤维细胞数(r = 0.65,P = 0.037)和活化纤维细胞数(r = 0.70,P = 0.016)呈显著相关。我们的数据表明,骨髓来源的循环纤维细胞与高血压性心脏病患者左心室肥厚的存在和程度有关。
Autopsy and biopsy studies have shown that there is significantly more fibrosis in hearts of patients with hypertensive heart disease compared to normal hearts. Fibrocytes, a population of circulating bone marrow-derived cells, have been shown to home to tissues and promote scar formation in several diseases, but their role in human hypertensive heart disease has not been investigated to date. Our objective was to determine whether fibrocyte levels are elevated in individuals with hypertensive heart disease. We measured peripheral blood fibrocyte levels and their activated phenotypes in 12 individuals with hypertensive heart disease as determined by increased left ventricular mass on noninvasive imaging and compared them to fibrocyte levels from 19 healthy normal controls and correlated them to cardiac MRI findings. Compared to normal controls, individuals with hypertensive heart disease had significantly higher circulating levels of total fibrocytes [median (interquartile range); 149000 (62200–220000) vs. 564500 (321000–1.2900e+006), P < 0.0001, respectively] as well as activated fibrocytes [15700 (6380–19800) vs. 478500 (116500–1.2360e+006) P < 0.0001]. Moreover, the fibrocyte subsets expressing the chemokine markers CXCR4 (P < 0.0001), CCR2 (P < 0.0001), CCR7 (P < 0.0001) and coexpression of both CXCR4 and CCR2 (P < 0.0001) were significantly elevated in patients with hypertensive heart disease compared to controls. Lastly, in patients with hypertensive heart disease there was a strong correlation between left ventricular mass index and total fibrocytes (r = 0.65, P = 0.037) and activated fibrocytes (r = 0.70, P = 0.016). Our data suggest that bone marrow-derived circulating fibrocytes are associated with the presence and extent of left ventricular hypertrophy in patients with hypertensive heart disease.