Periodic Reporting for period 1 - SPeR-ToNE (Spermidine in hypertension: therapeutic potential and novel mechanisms)
Reporting period: 2022-02-21 to 2024-02-20
Hypertension remains a leading risk factor for cardiovascular disease, posing major challenges to society and healthcare systems, as only one-third of patients effectively control their blood pressure with existing medications. Toward this end, growing evidence suggests that spermidine, a naturally occurring activator of the cellular housekeeping process, known as autophagy, is associated with lower blood pressure in humans. The project's major objective is to leverage this insight to examine whether spermidine, available as a dietary supplement, can be used to improve blood pressure and, if so, what the underlying mechanisms are.
In preliminary work, spermidine feeding to salt-sensitive hypertensive rats effectively attenuated high blood pressure. To evaluate the mechanisms, particularly autophagy, a mouse model with reduced autophagic capacity was generated. Subsequently, these mice and their wild-type controls were subjected to an experimental protocol of hypertension. However, this model, involving the use of a high-salt diet, failed to induce a sufficient rise in blood pressure, precluding the possibility of evaluating the crosstalk between autophagy, hypertension, and spermidine. Thus, the protocol needs to be modified, or other models need to be used to determine the role of autophagy in the blood pressure-lowering effect of spermidine, which went beyond the budget and timeframe of this project.
Spermidine supplementation is currently undergoing testing for its blood pressure-lowering effects in an ongoing clinical trial involving hypertensive patients. If patients demonstrate similar benefits to those observed in experimental models of the disease, this might lead to the launch of a new class of antihypertensive medications based on autophagy induction, paving the way for changes in patient treatment protocols. In fact, introducing a pluripotent compound, which not only counteracts hypertension but also slows aging at a systemic level, will have a significant impact on medicine as well as the economy. This could reduce the massive bill caused by hypertension, which is expected to continuously increase as lifespan extends, and our aging population grows.