Sildenafil Attenuates Persistent Pulmonary Hypertension of the Newborn via Inhibiting the Growth and Migration of Pulmonary Artery Smooth Muscle Cells
Abstract
INTRODUCTION
Sildenafil, a selective phosphodiesterase 5 inhibitor, modulates vascular dysfunction, with hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation, migration, and invasion closely implicated in vascular remodeling in persistent pulmonary hypertension of the newborn (PPHN). This study aimed to assess sildenafil's protective effects against PPHN and elucidate underlying molecular pathways.
METHODS
Cell Counting Kit-8, wound healing, and Transwell assays evaluated rat PASMC proliferation, migration, and invasion under hypoxia. A rat PPHN model assessed sildenafil's impact on right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), and vascular remodeling. JAK2/STAT3 signaling was analyzed via Western blotting.
RESULTS
Sildenafil significantly inhibited hypoxia-induced PASMC proliferation, migration, and invasion. In addition, sildenafil reduced RVSP, RVH, and vascular remodeling in PPHN. Further, sildenafil decreased JAK2 and STAT3 phosphorylation in hypoxia-exposed PASMCs and the PPHN rat model. The JAK2/STAT3 pathway agonist colivelin reversed sildenafil's suppressive effects on PASMC proliferation, migration, invasion, as well as RVSP, RVH, and vascular remodeling in PPHN.
CONCLUSIONS
Sildenafil protects against PPHN by inhibiting PASMC proliferation, migration, and invasion via suppression of JAK2/STAT3 signaling, indicating its potential as a therapeutic target for PPHN and contributing to a more comprehensive…
Read the paper
Related studies
- 2024 update in heart failure
- Vascular involvement in idiopathic pulmonary fibrosis
- A novel technique- subendometrial autologous platelet rich plasma injection in patients with unresponsive thin endometrium undergoing frozen-thawed embryo transfer: a prospective cohort study
- Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial
- Combined Pulmonary Fibrosis and Emphysema (CPFE): A "New" Smoking-Related Interstitial Lung Disease (ILD)
- Impact of an acute 1-month cannabidiol treatment on pain and inflammation after a long bone fracture: a triple-blind randomised, placebo-controlled, clinical trial protocol
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.