Pulmonary capillary endothelial metabolic dysfunction -: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension
Pulmonary capillary endothelial metabolic dysfunction -: Severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension
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DOI：
10.1002/art.23405
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发表时间：
2008-04-01
影响因子：
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通讯作者：
Catravas, John D.
中科院分区：
文献类型：
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作者：
Langleben, David;Orfanos, Stylianos E.;Catravas, John D.
Objective.肺内皮功能障碍与肺动脉高压（PAH）的发生和进展交织在一起。肺内皮细胞是健康人的活跃代谢组织。本研究旨在确定PAH对肺内皮血管紧张素转换酶（ACE）活性的影响，并确定常见PAH类型之间的差异，与结缔组织病相关的PAH（PAH-CTD）与特发性PAH（IPAH）。对19例PAH-CTD患者、25例IPAH患者和23例对照受试者进行了评价。测定ACE合成底物的单程透硫酸百分比代谢（%M）和水解（均反映每个毛细管的酶活性）。此外，计算的功能性毛细血管表面积（FCSA），归一化为体表面积（BSA），进行了测定。PAHCTD患者的%M值与对照受试者（P < 0.01）和IPAH患者（P < 0.03）相比，IPAH组（平均+/- SEM 53.6 +/- 3.6%）显著降低，但IPAH组和对照组之间相似（平均+/- SEM分别为66.2 +/- 3.6%和74.7 +/-2.7%）。PAH-CTD患者的底物水解也显著减少。PAH-CTD患者的FCSA/BSA（平均值± SEM 1，068 ± 118 ml/min/m2）和IPAH患者的FCSA/BSA（1，443 ± 186 ml/min/m2）与对照组（2，948 245 ml/min/m2; P < 0.01）相比显著降低。在给定的心脏指数下，PAH-CTD组的FCSA/BSA倾向于低于IPAH组。PAH-CTD组FCSA/BSA与一氧化碳弥散量（DLCO）呈线性相关（r = 0.54，P < 0.03）。PAH-CTD和IPAH的代谢功能性肺毛细血管床似乎在相同程度上减少。然而，%M和水解似乎在PAH-CTD中降低，但在IPAH中未降低，反映了PAH-CTD患者肺毛细血管内皮细胞上ACE活性相对降低，并表明肺内皮代谢功能在PAH类型之间存在差异。本研究还提供了第一个功能证据，表明PAH-CTD患者的DLCO值降低与FCSA丢失程度相关。
Objective. Pulmonary endothelial dysfunction is intertwined with the development and progression of pulmonary arterial hypertension (PAH). Pulmonary endothelium is an active metabolic tissue in healthy human subjects. This study was undertaken to determine the effects of PAH on pulmonary endothelial angiotensin-converting enzyme (ACE) activity and to identify differences between common PAH types, i.e., PAH related to connective tissue disease (PAH-CTD) versus idiopathic PAH (IPAH).Methods. Nineteen patients with PAH-CTD, 25 patients with IPAH, and 23 control subjects were evaluated. The single-pass transpulmonary percent metabolism (%M) and hydrolysis (both reflecting enzyme activity per capillary) of an ACE synthetic substrate were determined. In addition, the calculated functional capillary surface area (FCSA), normalized to body surface area (BSA), was determined.Results. The %M values in patients with PAHCTD (mean +/- SEM 53.6 +/- 3.6%) were significantly reduced compared with those in control subjects (P < 0.01) and those in patients with IPAH (P < 0.03), but were similar between the IPAH and control groups (mean +/- SEM 66.2 +/- 3.6% and 74.7 +/- 2.7%, respectively). Substrate hydrolysis was also significantly reduced in patients with PAH-CTD. The FCSA/BSA was significantly reduced in patients with PAH-CTD (mean +/- SEM 1,068 +/- 118 ml/minute/m(2)) and in patients with IPAH (1,443 +/- 186 ml/minute/m(2)) compared with that in controls (2,948 245 ml/minute/m2; P < 0.01 for both). At a given cardiac index, the FCSA/BSA tended to be lower in the PAH-CTD group than in the IPAH group. Moreover, unlike in IPAH, a linear relationship between the FCSA/BSA and the diffusing capacity for carbon monoxide (DLCO) was observed in PAH-CTD (r = 0.54, P < 0.03).Conclusion. The metabolically functional pulmonary capillary bed appears to be reduced to an equal extent in PAH-CTD and IPAH. However, %M and hydrolysis appear to be reduced in PAH-CTD but not in IPAH, reflecting relatively diminished ACE activity on the pulmonary capillary endothelial cells of patients with PAH-CTD, and showing that pulmonary endothelial metabolic function differs between PAH types. This study also provides the first functional evidence that a reduced DLCO value in patients with PAH-CTD is related to the degree of FCSA loss.