Plexiform Lesions in Pulmonary Arterial Hypertension Composition, Architecture, and Microenvironment
Plexiform Lesions in Pulmonary Arterial Hypertension Composition, Architecture, and Microenvironment
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DOI：
10.1016/j.ajpath.2011.03.040
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发表时间：
2011-07-01
影响因子：
6
通讯作者：
Laenger, Florian
中科院分区：
文献类型：
--
作者：
Jonigk, Danny;Golpon, Heiko;Laenger, Florian
肺动脉高压（PAH）是一种致残性疾病，死亡率高。多环芳烃的一个特征是网状病变（PLs），起源于肺动脉重塑的复杂血管形成。这些病变的发展和意义一直存在争议，尚未完全理解。PLs的一些特征类似于肿瘤疾病，并且与胶质母细胞瘤中的肾小球样病变（gll）有惊人的相似之处。为了进一步阐明PLs，我们使用了原位方法，如（荧光）免疫组化染色，三维重建和激光显微解剖，然后进行mRNA表达分析。我们在25例患者（11例PAH合并全身分流，6例特发性PAH， 8例对照）和5例胶质母细胞瘤的gll中生成了室特异性表达模式。PLs由连续增殖的内皮细胞和均匀的肌间质构成的血管通道组成。它们还显示了重构相关基因的上调，如HIF1a、tgf - β 1、vegf - α、VEGFR-1/ 2、Ang-1、Tie-2和THRS1，以及cKIT和发芽相关标记，如NOTCH和基质金属蛋白酶。神经肿瘤中gll的细胞组成和信号传导与PLs明显不同。总之，PLs具有独特的细胞组成和微环境，这有助于形成丛状表型，并将其与PAH患者的其他血管重塑过程区分开来。血管生成的肿瘤模型在丛状血管病变的进一步研究中似乎应用有限。（Am Pathol-112011, 179:167-179; DOI: 10.1016/ j.j ajpath.2011.03.040）
Pulmonary arterial hypertension (PAH) is a debilitating disease with a high mortality rate. A hallmark of PAH is plexiform lesions (PLs), complex vascular formations originating from remodeled pulmonary arteries. The development and significance of these lesions have been debated and are not yet fully understood. Some features of PLs resemble neoplastic disorders, and there is a striking resemblance to glomeruloid-like lesions (GLLs) in glioblastomas. To further elucidate PLs, we used in situ methods, such as (fluorescent) IHC staining, three-dimensional reconstruction, and laser microdissection, followed by mRNA expression analysis. We generated compartment-specific expression patterns in the lungs of 25 patients (11 with PAH associated with systemic shunts, 6 with idiopathic PAH, and 8 controls) and GLLs from 5 glioblastomas. PLs consisted of vascular channels lined by a continuously proliferating endothelium and backed by a uniform myogenic interstitium. They also showed up-regulation of remodeling-associated genes, such as HIF1a, TGF-beta 1, VEGF-alpha, VEGFR-1/-2, Ang-1, Tie-2, and THRS1, but also of cKIT and sprouting-associated markers, such as NOTCH and matrix metalloproteinases. The cellular composition and signaling seen in GLLs in neural neoplasms differed significantly from those in PLs. In conclusion, PLs show a distinct cellular composition and microenvironment, which contribute to the plexiform phenotype and set them apart from other processes of vascular remodeling in patients with PAH. Neoplastic models of angiogenesis seem to be of limited use in further study of plexiform vasculopathy. (Am Pathol-112011, 179:167-179; DOI: 10.1016/j.ajpath.2011.03.040)