Capsaicin Receptor Activation Slows Aortic Aging in Atherosclerosis by Targeting ISG15-p53

Aortic aging is a significant contributor to cardiovascular diseases, particularly in the context of atherosclerosis, where it exacerbates vascular dysfunction and increases morbidity. The transient receptor potential cation channel subfamily V member 1 (TRPV1), commonly known as the capsaicin receptor, is a non-selective cation channel involved in various physiological processes, including pain perception and inflammation. While TRPV1 has been implicated in vascular health, its precise role in mitigating aortic aging under atherosclerotic conditions and the underlying molecular mechanisms have remained largely unexplored. This study addresses this knowledge gap by investigating whether activating TRPV1 can attenuate aortic aging in atherosclerotic mice and elucidating the involvement of the ISG15-p53 signaling pathway.

The investigation revealed that TRPV1 activation significantly attenuated several critical markers of aortic aging in the atherosclerotic mouse model when compared to untreated control groups. Specifically, treated mice exhibited a marked reduction in cellular senescence, a process where cells stop dividing but remain metabolically active, contributing to aging. This was accompanied by improved endothelial function, indicating healthier blood vessel linings. > The most pivotal finding was that TRPV1 activation led to a substantial decrease in the expression of ISG15 (interferon-stimulated gene 15) and a subsequent inhibition of p53 activation, demonstrating a direct molecular pathway for its anti-aging effects. This inhibition of the ISG15-p53 pathway was quantitatively associated with a significant improvement in aortic elasticity and a reduction in pro-inflammatory cytokine levels, collectively pointing towards a comprehensive protective effect against age-related vascular deterioration.