Abstract 668: Myeloid Pfkfb3 Deficiency Protect Mice From Hypoxia Induced Pulmonary Hypertension

Abstract

Background: Pulmonary hypertension is a progressive disease and perivascular inflammation is found in all types of pulmonary hypertension patients. Macrophage are innate inflammatory cells and the number of macrophages are significantly increased in the lungs of PAH patients. Glycolysis is the main pathway to generate energy and intermediate products for macrophage activation. However, the effect of macrophage glycolysis on the development of pulmonary hypertension remains unknown. As PFKFB3 is a critical regulator in glycolysis, we investigated the effect of macrophage glycolysis on pulmonary hypertension using myeloid PFKFB3 specific deficiency mice and hypoxia induced pulmonary hypertension model. Results: In mouse and rat hypoxia induced pulmonary hypertension models, we found that PFKFB3 was upregulated in macrophages. PFKFB3 myeloid specific depletion protected mice from the formation of pulmonary hypertension. Knockdown of PFKFB3 in macrophages suppressed the expression of growth factors and inflammatory cytokines in whole lung tissue. Also, we found that PFKFB3 knockdown decreased the numbers of perivascular macrophages and interstitial macrophages using immunostaining and FACS. The number of alveolar macrophages showed no significant difference, while the expression of growth factors and inflammatory cytokines were decreased in alveolar macrophage when PFKFB3 was depleted. Conclusions: PFKFB3 depletion in macrophage decreases the number of perivascular macrophages and interstitial macrophages in the lung, and suppresses the expression of growth factors and inflammatory cytokines in alveolar macrophage, thus protecting mice from the formation of pulmonary hypertension.