Relevant issues in the pathology and pathobiology of pulmonary hypertension.
Relevant issues in the pathology and pathobiology of pulmonary hypertension.
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DOI：
10.1016/j.jacc.2013.10.025
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发表时间：
2013-12-24
影响因子：
24
通讯作者：
Morrell, Nicholas W.
中科院分区：
文献类型：
--
作者：
Tuder, Rubin M.;Archer, Stephen L.;Dorfmueller, Peter;Erzurum, Serpil C.;Guignabert, Christophe;Michelakis, Evangelos;Rabinovitch, Marlene;Schermuly, Ralph;Stenmark, Kurt R.;Morrell, Nicholas W.
对肺动脉高压病理生物学的了解不断增加。然而，我们对不同形式的肺动脉和肺静脉的潜在病理变化的理解仍然存在根本的差距。虽然肺动脉高压主要影响动脉，但静脉疾病越来越被认为是一个重要的实体。此外，肺动脉高压的预后主要取决于右心室的状态，而不是肺动脉压的水平。越来越清楚的是，在血管痉挛起作用的同时，肺动脉高压是一种阻塞性肺全血管病变。代谢和线粒体结构紊乱、炎症和生长因子失调导致增殖、细胞凋亡抵抗状态。这些异常可能是获得性的，遗传介导的结果是骨形态发生蛋白受体（BMPR）2或激活素样激酶(Alk)-1突变或表观遗传遗传（由于表观遗传沉默的基因，如超氧化物歧化酶2）。迫切需要更好地了解病理生物学是如何导致一些患者出现严重疾病而另一些患者出现轻度肺动脉高压的。最近认识到右室肌细胞和肺血管细胞获得性线粒体代谢异常的潜在作用，提出了新的治疗方法、诊断方式和生物标志物。最后，肺部炎症在肺动脉高压发生和促进中的作用揭示了肺动脉高压与肺血管重构之间复杂而有趣的相互作用，有望带来新的治疗和诊断方法。新兴概念也与肺动脉高压的病理生物学有关，包括骨髓和循环祖细胞和microrna的作用。继续关注肺动脉高压的遗传基础和细胞和分子发病联系的界面，应该进一步扩大我们对这种疾病的理解。
Knowledge of the pathobiology of pulmonary hypertension continues to accelerate. However, fundamental gaps remain in our understanding of the underlying pathological changes in pulmonary arteries and veins in the different forms of this syndrome. Although pulmonary hypertension primarily affects the arteries, venous disease is increasingly recognized as an important entity. Moreover, prognosis in pulmonary hypertension is determined largely by the status of the right ventricle, rather than the levels of pulmonary artery pressures. It is increasingly clear that while vasospasm plays a role, pulmonary hypertension is an obstructive lung panvasculopathy. Disordered metabolism and mitochondrial structure, inflammation, and dysregulation of growth factors lead to a proliferative, apoptosis-resistant state. These abnormalities may be acquired, genetically mediated as a result of mutations in bone morphogenetic protein receptor (BMPR)2 or activin-like kinase (Alk)-1 or epigenetically-inherited (as a result of epigenetic silencing of genes such as superoxide dismutase 2). There is a pressing need to better understand how the pathobiology leads to severe disease in some patients versus mild pulmonary hypertension in others. Recent recognition of a potential role of acquired abnormalities of mitochondrial metabolism in the right ventricular myocytes and pulmonary vascular cells suggests new therapeutic approaches, diagnostic modalities, and biomarkers. Finally, dissection of role of pulmonary inflammation in the initiation and promotion of pulmonary hypertension has revealed a complex yet fascinating interplay with pulmonary vascular remodeling, promising to lead to novel therapeutics and diagnostics. Emerging concepts are also relevant to the pathobiology of pulmonary hypertension, including a role for bone marrow and circulating progenitor cells and microRNAs. Continued interest in the interface of the genetic basis of pulmonary hypertension and cellular and molecular pathogenetic links should expand further our understanding of the disease.
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影响因子：
10
作者：
Chaouat, A;Coulet, F;Humbert, M
通讯作者：
Humbert, M
影响因子：
20.3
作者：
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通讯作者：
Erzurum, Serpil C.
影响因子：
6
作者：
Fijalkowska, Iwona;Xu, Weiling;Tuder, Rubin M.
通讯作者：
Tuder, Rubin M.
影响因子：
16.8
作者：
Buckley, CD;Pilling, D;Salmon, M
通讯作者：
Salmon, M
DOI：
10.1152/ajplung.2000.278.5.l981
发表时间：
2000-05-01
影响因子：
4.9
作者：
Aguirre, JI;Morrell, NW;Wilkins, MR
通讯作者：
Wilkins, MR