Abstract 14914: Vascular Remodelling Can Be Alleviated by Stem Cell Exosomes in Pulmonary Arterial Hypertension via HIF-1α and Runx2 Signalling Pathway
Mei-Tzu Wang, Kun-Chang LIN, Wei-Chun Huang- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Introduction: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared to the induced pluripotent stem cells (iPSCs).
Hypothesis: In this study, we determined the efficacy and mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension.
Methods: Both prophylactic and therapeutic iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats.
Results: Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and PAK1/AKT/Runx2 pathways.
Conclusions: IPSC-Exo are effective at preventing and reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.