Abstract
The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. ApoA-I null (apoA-I(-/-)) mice had reduced total and HDL cholesterol but increased pro-inflammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I(-/-) mice, PON1 activity was decreased. ApoA-I deficiency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I(-/-) mice, a finding also confirmed by positive end-expiratory pressure (PEEP) studies. Inflammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I(-/-) lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor beta-1 (TGFbeta-1 was increased in apoA-I(-/-) lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I(-/-) lungs. Dichlorodihydrofluorescein-detectable oxidants were increased in bronchoalveolar lavage fluid (BALF) in apoA-I(-/-) mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I(-/-) mice. These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness.
Highlights
The relationship between high-density lipoprotein and pulmonary function is unclear
In this article we examine the effects of genetic deletion of apolipoprotein A-I (apoA-I) on pulmonary inflammation, vasodilatation, collagen deposition, and airway hyperresponsiveness
Effects of apoA-I deficiency on lipids and oxidative stress ApoA-IϪ/Ϫ mice had reduced levels of plasma total cholesterol and HDL cholesterol compared with control mice (Fig. 1A, B)
Summary
The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. BALF nitrite+nitrate levels were decreased in apoA-IϪ/Ϫ mice These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness.—Wang, W., H. Genetic deletion of endothelial lipase resulted in a nearly 2-fold increase in HDL, which was credited with decreasing airway hyperresponsiveness and pulmonary inflammation in ovalbumin (OVA)-sensitized BALB/c mice [3]. These reports provide some support for the idea that HDL helps maintain healthy lungs, no studies have directly determined the effects of apoA-I, or lack thereof, on pulmonary inflammation, vasodilatation, and airway hyperresponsiveness
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