Breakthrough in Cell Signaling Pathway Offers New Hope for Protecting Blood Vessels from Hypertension Damage

Researchers at Lund University in Sweden have identified a novel cell signaling pathway that could play a crucial role in safeguarding blood vessels from damage caused by high blood pressure, or hypertension. By artificially inducing aging in mice, the team was able to observe the development of aneurysms within blood vessel walls, providing insights into the molecular changes associated with vascular aging.

A surprising discovery emerged when the scientists activated an alternative signaling pathway in the vessel wall cells, which paradoxically protected the mice from hypertension-related damage. This finding suggests potential for future therapeutic strategies centered on enhancing this protective pathway in humans.

The study focused on the declining activity of the serum response factor (SRF), a key transcription factor controlling gene expression in vascular smooth muscle cells. When SRF was knocked out in mice, early aneurysm-like structures formed rapidly, mimicking human vascular aging and disease. Interestingly, the activation of the YAP/TAZ pathway, known for its role in cell growth and organ size regulation, was observed as a compensatory mechanism when SRF activity decreased. This interplay is mediated by the enzyme LATS2, which typically inhibits YAP/TAZ activity; its reduction allows YAP/TAZ to flourish, helping maintain vessel integrity.

In earlier research, the team found that proteins YAP and TAZ decrease with age, leading to weakened vessel walls and increased susceptibility to aneurysm formation. The current findings reveal that when SRF activity drops, YAP/TAZ activation offers a protective effect, potentially offsetting the adverse effects of vascular aging. This novel insight paves the way for developing targeted drugs that inhibit LATS2, with the goal of strengthening blood vessels and preventing damage from hypertension.

The researchers emphasize that while these findings are promising, developing specific inhibitors targeting LATS2 could take at least five years. Nonetheless, this discovery opens up exciting possibilities for creating complementary blood pressure medicines that focus not only on lowering pressure but also on reinforcing vessel structure. The findings also contribute deeper understanding of how blood vessels adapt to the mechanical forces exerted by blood flow, especially during aging.

The study, titled "Declining activity of serum response factor in aging aorta in relation to aneurysm progression," was led by Associate Professor Catarina Rippe and Professor Karl Swärd. Their work highlights the complex molecular communications within blood vessel cells and offers hope for future interventions to reduce the risk of vascular diseases associated with aging and hypertension.