Hypoxia-Induced Fractalkine-Stimulated Endothelial/Pericyte Dynamics In Pulmonary Hypertension
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2016)
Abstract
Distal vascular remodeling is a hallmark of hypoxic pulmonary hypertension (PH). The capillary walls of the pulmonary non-muscular microvessels consist of endothelial cells and pericytes. Since hypoxia stimulates overproduction of a unique chemokine/fractalkine, CX3CL1 and pericytes functions as contractile elements within the microvasculature, this study is focused to identify the role of CX3CL1 and its sole receptor CX3CR1 axis in hypoxia-induced endothelial/pericyte dynamics in pulmonary pathophysiology. Hypoxia-induced release of CX3CL1 from mouse lung microvascular endothelial cell (MVEC) enhanced proliferation of pericytes. Treatments with CX3CL1 neutralizing antibody or CX3CR1 antagonist attenuated recombinant CX3CL1 (rCX3CL1)-mediated pericyte proliferation. Direct interaction of increasing levels of pericyte with MVEC attenuated MVEC function assessed by acetylcholine (Ach)-stimulated nitric oxide (NO)/cGMP levels. Hypoxia exposure increased pericyte expression in the lungs of wild-type (WT) but not in CX3CR1 knockout (KO) mice. Echocardiographic assessment of hypoxia-induced pulmonary hemodynamic changes indicated decreased pulmonary acceleration time (PAT) and PAT/ejection time (PET) in WT hypoxic as compared to WT normoxic mice. However, PAT and PAT/PET in CX3CR1 KO hypoxic and normoxic mice were comparable to WT normoxic mice. Assessment of RV free wall thickness indicated increases in hypoxic WT but not in CX3CR1 KO mice. These results indicate that hypoxia-induced elevation of CX3CL1 increased pericyte proliferation leading to MVEC dysfunction and altered pulmonary hemodynamics consistent with the pathophysiologic changes observed in the development of PH.
MoreTranslated text
Key words
Hypoxia, fractalkine, lung, endothelium, pericyte, hypertension
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined