R-Propranolol Promotes the Adipogenesis and Subsequent Apoptosis of Hemangioma Stem Cells through the Protein Kinase...

Area of Science:

• Vascular Biology
• Cellular Signaling
• Pharmacology

Background:

• Infantile hemangioma (IH) is commonly treated with propranolol, but adverse effects limit its use.
• R-propranolol, a non-beta-blocking enantiomer, shows potential as an alternative IH therapy.
• The protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway is implicated in hemangioma stem cell (HemSC) behavior.

Purpose of the Study:

• To investigate the efficacy of R-propranolol in infantile hemangioma (IH) involution.
• To elucidate the underlying mechanism of R-propranolol's action on hemangioma stem cells (HemSCs).

Main Methods:

• Comparing R-propranolol and racemic propranolol effects on HemSC adipogenesis and apoptosis.
• Assessing protein homeostasis disruption and PERK pathway activation by R-propranolol.
• Utilizing a PERK inhibitor (GSK2606414) to confirm pathway involvement.
• Analyzing PERK expression in clinical IH samples.

Main Results:

• R-propranolol and racemic propranolol induced comparable HemSC adipogenesis.
• R-propranolol more effectively disrupted protein homeostasis and activated the PERK pathway in HemSCs.
• R-propranolol induced greater HemSC apoptosis, an effect reversed by a PERK inhibitor.
• Higher PERK expression was observed in involuting IH compared to proliferating IH.

Conclusions:

• R-propranolol promotes HemSC adipogenesis and subsequent apoptosis via PERK pathway activation.
• R-propranolol demonstrates a potent mechanism for infantile hemangioma (IH) involution.
• R-propranolol represents a promising therapeutic agent for IH, potentially with an improved safety profile.