The Platelet-Derived Growth Factor Pathway in Pulmonary Arterial Hypertension: Still an Interesting Target?

Life

卷:12

Jonathan Ribot¹  Florent Soubrier¹  Julien Solinc¹  Sophie Nadaud¹  Catherine Pavoine¹  France Dierick² 

[1] INSERM, Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, UMR_S1166, F-75013 Paris, France;

[2] Lady Davis Institute for Medical Research, McGill University, Montreal, QC H3T 1E2, Canada;

关键词: PDGF;    PDGFR;    smooth muscle cells;    fibroblast;    pulmonary arterial hypertension;    vascular remodeling;   

DOI  :  10.3390/life12050658

来源: DOAJ

【 摘 要 】

The lack of curative options for pulmonary arterial hypertension drives important research to understand the mechanisms underlying this devastating disease. Among the main identified pathways, the platelet-derived growth factor (PDGF) pathway was established to control vascular remodeling and anti-PDGF receptor (PDGFR) drugs were shown to reverse the disease in experimental models. Four different isoforms of PDGF are produced by various cell types in the lung. PDGFs control vascular cells migration, proliferation and survival through binding to their receptors PDGFRα and β. They elicit multiple intracellular signaling pathways which have been particularly studied in pulmonary smooth muscle cells. Activation of the PDGF pathway has been demonstrated both in patients and in pulmonary hypertension (PH) experimental models. Tyrosine kinase inhibitors (TKI) are numerous but without real specificity and Imatinib, one of the most specific, resulted in beneficial effects. However, adverse events and treatment discontinuation discouraged to pursue this therapy. Novel therapeutic strategies are currently under experimental evaluation. For TKI, they include intratracheal drug administration, low dosage or nanoparticles delivery. Specific anti-PDGF and anti-PDGFR molecules can also be designed such as new TKI, soluble receptors, aptamers or oligonucleotides.

【 授权许可】

Unknown