2015年3月19日文献精读摘要

作者：TeachingAssistant 来源：日期：2015/3/13 23:19:26 人气：

Am J Respir Crit Care Med. 2015 Jan 15;191(2):208-18. doi: 10.1164/rccm.201409-1742OC.

Serum endostatin is a genetically determined predictor of survival in pulmonary arterial hypertension.

Damico R1, Kolb TM, Valera L, Wang L, Housten T, Tedford RJ, Kass DA, Rafaels N, Gao L, Barnes KC, Benza RL, Rand JL, Hamid R, Loyd JE, Robbins IM, Hemnes AR, Chung WK, Austin ED, Drummond MB, Mathai SC, Hassoun PM.

RATIONALE:

Pulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH.

OBJECTIVES:

We sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH.

METHODS:

We measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minute-walk distance, invasive hemodynamics, and laboratory chemistries.

MEASUREMENTS AND MAIN RESULTS:

Serum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality.

CONCLUSIONS:

Our data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.

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2015年3月19日文献精读摘要

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