RAGE Pathway Involved in CTEPH and iPAH Provides New Therapeutic Targets

RAGE Pathway Involved in CTEPH and iPAH Provides New Therapeutic Targets

shutterstock_202549273New insights into the molecular mechanisms of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) generally lead to new avenues of research for treatments that may work better than existing treatments or open the doors for previously untreatable patients. Work from Medical University Vienna in Austria, published in the journal PLoS One, established a relationship between the receptor for advanced glycation endproducts (RAGE) pathway and CTEPH/iPAH.

In the study, “Local and Systemic RAGE Axis Changes in Pulmonary Hypertension: CTEPH and iPAH,” specimens obtained from 26 CTEPH, 15 iPAH, and 15 aortic valve stenosis patients and 33 healthy volunteers were used to establish the connection. Serum levels of sRAGE, esRAGE, and HMGB1 (all molecules in the RAGE pathway involved in inflammation) were elevated in patients with CTEPH, and sRAGE and esRAGE were elevated in iPAH patients, with sRAGE higher in iPAH than CTEPH. Interestingly, sRAGE was lower in aortic valve stenosis patients than in healthy volunteers.

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RAGE proteins were expressed in prototypical Heath Edwards lesions in iPAH patients and in endarterectomised tissues from CTEPH patients. These biomarkers were unchanged following surgery to correct for CTEPH, iPAH, or aortic valve stenosis, indicating that surgery does not improve the systemic inflammation of patients.

A handful of RAGE inhibitors are currently under evaluation for other immune-linked diseases such as Alzheimer’s Disease and diabetes. At least nine clinical trials are registered for RAGE inhibitors, indicating that it may be relatively less burdensome to initiate RAGE inhibitor treatment for pulmonary hypertension. Indeed, further studies must first be conducted, but these recent findings may now lead RAGE inhibitors to represent a new vanguard in treatment for both CTEPH and iPAH.

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