NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling.

Arterioscler Thromb Vasc Biol

From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.

Published: August 2014

Objective: Pulmonary hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PAs) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PAs and determine the functional relevance of Nox4 in PH.

Approach And Results: Elevated expression of Nox4 was detected in hypertensive PAs from 3 rat PH models and human PH using qualititative real-time reverse transcription polymerase chain reaction, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia, and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of reactive oxygen species production. Small-molecule inhibitors of Nox4 reduced adventitial reactive oxygen species generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and noninvasive indices of PA stiffness in monocrotaline-treated rats as determined by morphometric analysis and high-resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PAs. In fibroblasts, Nox4 overexpression stimulated migration and proliferation and was necessary for matrix gene expression.

Conclusion: These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling, and development of PH.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228789PMC
http://dx.doi.org/10.1161/ATVBAHA.114.303848DOI Listing

Publication Analysis

Top Keywords

vascular remodeling
16
reactive oxygen
12
oxygen species
12
nox4
10
nadph oxidase
8
adventitia contributes
8
hypertensive vascular
8
cells expressing
8
nox4 detected
8
vascular
6

Similar Publications

This study investigated the sexual dimorphism in right ventricle (RV) remodeling in right heart failure susceptible Fischer CDF rats using the pulmonary artery banding (PAB) model. Echocardiography and hemodynamic measurements were performed in adult male and female Fischer CDF rats at 1- or 2-weeks post-PAB. RV systolic pressure and RV hypertrophy were significantly elevated in PAB rats compared to sham control at 1- and 2-weeks post-PAB; however, no differences were observed between male and female rats.

View Article and Find Full Text PDF

Quantification of Vascular Remodeling and Sinusoidal Capillarization to Assess Liver Fibrosis with Photoacoustic Imaging.

Radiology

January 2025

From the Department of Radiology, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics, Guangdong Province), Guangzhou, China (W.L., L.S., R.Z., Y.Z.); and Medical Research Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Zhongshan 2nd Rd, Yuexiu District, Guangzhou 510000, People's Republic of China (J.L., H.L., X.Z., F.X., T.S., K.L., L.N.).

Background Photoacoustic microscopy (PAM) can be used to detect strong absorption from endogenous and exogenous contrast material, making it promising for detailed structural and functional imaging of hepatic sinusoids, including dynamic visualization of permeability. Purpose To evaluate whether PAM-based quantitative parameters of liver function and integrity (lacunarity, blood oxygen saturation [Sao], and Evans blue [EB] permeability) are associated with histopathologic indexes of fibrosis in a mouse model. Materials and Methods Between October 2022 and July 2023, a total of 35 male C57BL/6 mice were included in this study and received intraperitoneal injection of carbon tetrachloride to establish mouse models of progressive liver fibrosis, with seven mice in each group.

View Article and Find Full Text PDF

Glycocalyx disruption, endothelial dysfunction and vascular remodeling as underlying mechanisms and treatment targets of chronic venous disease.

Int Angiol

December 2024

Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA -

The glycocalyx is an essential structural and functional component of endothelial cells. Extensive hemodynamic changes cause endothelial glycocalyx disruption and vascular dysfunction, leading to multiple arterial and venous disorders. Chronic venous disease (CVD) is a common disorder of the lower extremities with major health and socio-economic implications, but complex pathophysiology.

View Article and Find Full Text PDF

Osteoporosis under psychological stress: mechanisms and therapeutics.

Life Med

February 2024

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.

Psychological stress has been associated with the onset of several diseases, including osteoporosis. However, the underlying pathogenic mechanism remains unknown, and effective therapeutic strategies are still unavailable. Growing evidence suggests that the sympathetic nervous system regulates bone homeostasis and vascular function under psychological stress, as well as the coupling of osteogenesis and angiogenesis in bone development, remodeling, and regeneration.

View Article and Find Full Text PDF

A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.

Life Med

February 2024

Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China.

In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!