Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation.

This study investigated whether hexarelin, a synthetic growth hormone-releasing peptide, could reduce the development of abdominal aortic aneurysm (AAA) using an elastase-induced mouse model. Mice received hexarelin injections twice daily, and outcomes were assessed via echocardiography, in situ imaging, histology, and molecular analyses. The study found that hexarelin-treated mice showed reduced infrarenal aortic diameter and improved elastin integrity compared to untreated controls. At the cellular level, hexarelin appeared to preserve smooth muscle cell (SMC) contractile phenotype, evidenced by increased α-SMA expression and decreased MMP2. Additionally, hexarelin was associated with reduced inflammatory cell infiltration, suppression of NLRP3 inflammasome activation, lower IL-18 production, and inhibition of the NF-κB signaling pathway. The authors concluded that hexarelin attenuates AAA development by targeting SMC phenotype switching and NF-κB-mediated inflammation. Key limitations include the exclusive use of an animal model, meaning findings have not been validated in humans, and the mechanistic conclusions are based on a single preclinical model that may not fully replicate human AAA pathophysiology.

Why this grade: The study was conducted entirely in a mouse elastase-induced AAA model with no human subjects or clinical data, limiting direct translation of findings to humans.