Hexarelin Protects Against Abdominal Aortic Aneurysms by Stabilizing Smooth Muscle Cells

Hexarelin, a synthetic growth hormone-releasing peptide, has demonstrated protective effects in various cardiovascular diseases like myocardial infarction and atherosclerosis. These beneficial actions suggest its potential in mitigating vascular pathologies. However, its specific functional role in the development and progression of abdominal aortic aneurysm (AAA), a life-threatening condition characterized by arterial wall weakening, has remained largely unexplored and undefined.

The study revealed that Hexarelin administration significantly decreased the infrarenal aorta diameter in the mouse model, as observed through echocardiography and in situ imaging, indicating a clear reduction in aneurysm expansion compared to controls. Histological analysis further showed that Hexarelin markedly improved elastin degradation, a critical pathological feature of AAA progression. The most pivotal finding was that Hexarelin effectively rescued the smooth muscle cell (SMC) contractile phenotype, evidenced by a substantial increase in α-SMA (a marker of healthy, contractile SMCs) and a significant decrease in MMP2 (a matrix metalloproteinase that degrades extracellular matrix). Furthermore, Hexarelin powerfully inhibited inflammatory cell infiltration, suppressed NLRP3 inflammasome activation (a key inflammatory complex), and reduced IL-18 production. Critically, it also suppressed the NF-κB signaling pathway, a central regulator of inflammatory gene expression, thereby mitigating the overall inflammatory response. While specific numerical percentages or p-values were not provided in the abstract, the reported effects were consistently described as significant.