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Am J Physiol Heart Circ Physiol. 2013 Jul 15;305(2):H155-62. doi: 10.1152/ajpheart.00169.2012. Epub 2013 May 17.

Oxidative stress augments pulmonary hypertension in chronically hypoxic mice overexpressing the oxidized LDL receptor.

Author information

1
Departments of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. saogura-tky@umin.ac.jp

Abstract

Chronic hypoxia is one of the main causes of pulmonary hypertension (PH) associated with ROS production. Lectin-like oxidized low-density lipoprotein receptor (LOX)-1 is known to be an endothelial receptor of oxidized low-density lipoprotein, which is assumed to play a role in the initiation of ROS generation. We investigated the role of LOX-1 and ROS generation in PH and vascular remodeling in LOX-1 transgenic (TG) mice. We maintained 8- to 10-wk-old male LOX-1 TG mice and wild-type (WT) mice in normoxia (room air) or hypoxia (10% O2 chambers) for 3 wk. Right ventricular (RV) systolic pressure (RVSP) was comparable between the two groups under normoxic conditions; however, chronic hypoxia significantly increased RVSP and RV hypertrophy in LOX-1 TG mice compared with WT mice. Medial wall thickness of the pulmonary arteries was significantly greater in LOX-1 TG mice than in WT mice. Furthermore, hypoxia enhanced ROS production and nitrotyrosine expression in LOX-1 TG mice, supporting the observed pathological changes. Administration of the NADPH oxidase inhibitor apocynin caused a significant reduction in PH and vascular remodeling in LOX-1 TG mice. Our results suggest that LOX-1-ROS generation induces the development and progression of PH.

KEYWORDS:

NADPH oxidase; hypoxia; low-density lipoprotein receptor-1; oxidative stress; pulmonary hypertension

PMID:
23686713
DOI:
10.1152/ajpheart.00169.2012
[Indexed for MEDLINE]
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