Hypoxic vascular response and ventilation/perfusion matching in end-stage COPD may depend on p22phox

被引：17

作者：

Nagaraj, Chandran ^{[1
,2
]}

Tabeling, Christoph ^{[3
]}

Nagy, Bence M. ^{[1
,2
]}

Jain, Pritesh P. ^{[1
]}

Marsh, Leigh M. ^{[1
]}

Papp, Rita ^{[1
]}

Pienn, Michael ^{[1
]}

Witzenrath, Martin ^{[3
]}

Ghanim, Bahil ^{[4
]}

Klepetko, Walter ^{[4
]}

Weir, E. Kenneth ^{[5
]}

Heschl, Stefan ^{[6
]}

Kwapiszewska, Grazyna ^{[1
,2
]}

Olschewski, Andrea ^{[1
,2
]}

Olschewski, Horst ^{[1
,7
]}

机构：

[1] Ludwig Boltzmann Inst Lung Vasc Res, Graz, Austria

[2] Med Univ Graz, Inst Physiol, Graz, Austria

[3] Charite Univ Med Berlin, Dept Infect Dis & Pulm Med, Berlin, Germany

[4] Med Univ Vienna, Dept Thorac Surg, Div Surg, Vienna, Austria

[5] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA

[6] Med Univ Graz, Dept Anaesthesiol & Intens Care Med, Graz, Austria

[7] Med Univ Graz, Dept Internal Med, Div Pulmonol, Graz, Austria

来源：

EUROPEAN RESPIRATORY JOURNAL | 2017年 / 50卷 / 01期

关键词：

PULMONARY-HYPERTENSION; NADPH OXIDASES; SMOOTH-MUSCLE; NOX FAMILY; LUNG; VASOCONSTRICTION; CA2+; SUPEROXIDE; INHIBITION; MECHANISMS;

D O I：

10.1183/13993003.01651-2016

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease in which the amount of emphysema and airway disease may be very different between individuals, even in end-stage disease. Emphysema formation may be linked to the involvement of the small pulmonary vessels. The NAPDH oxidase (Nox) family is emerging as a key disease-related factor in vascular diseases, but currently its role in hypoxia-induced pulmonary remodelling in COPD remains unclear. Here we investigate the role of p22phox, a regulatory subunit of Nox, in COPD lungs, hypoxic pulmonary vasoconstriction (HPV), hypoxia-induced pulmonary vascular remodelling and pulmonary hypertension. In COPD, compared to control lungs, p22phox expression was significantly reduced. The expression was correlated positively with mean pulmonary arterial pressure and oxygenation index and negatively with the diffusing capacity of the lung for carbon monoxide (p<0.02). This suggests a role of p22phox in ventilation/perfusion ratio matching, vascular remodelling and loss of perfused lung area. In p22phox(-/-) mice, HPV was significantly impaired. In the chronic hypoxic setting, lack of p22phox was associated with improved right ventricular function and decreased pulmonary vascular remodelling. p22phox-dependent Nox plays an important role in the COPD phenotype, by its action on phase II HPV and chronic vascular remodelling.

引用

页数：13

共 38 条

[1] Direct interaction of the novel nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase [J].