3.3.3 Antiferroptosis may be a new target for hypertension
treatment in the future
Nrf2
can activate the transcription of target antioxidant genes and play a
key role in the oxidation reduction reaction regulation of
hypertension95. Studies have found that inhibiting
Nrf2 can promote oxidative stress and inflammation, and further
aggravate hypertension in mice96. On the contrary, it
promoted Nrf2 signaling pathway transduction and alleviated renal
ferroptosis and lipid peroxidation in hypertensive
state97. It was also found that activation of Nrf2
inhibited the progression of hypertension in hypertensive mice 12-14
days after infusion of Ang II98 . At present, studies
on Nrf2 in the development and progression of hypertension are limited.
Whether Nrf2 can protect hypertension by regulating related mechanisms
to inhibit ferroptosis needs more research to determine.
It was also found that
ferrostatin-1 administration
could reverse the ferroptosis of VSMCs induced by high hydrostatic
pressure7, while also significantly ameliorating
hypertension and endothelial ferroptosis induced by lenvatinib in
mice13 . This suggests that ferrostatin-1 may
alleviate hypertension by inhibiting ferroptosis of VSMCs and
endothelial cells, but it has not been applied in the clinic so far, and
more in-depth and comprehensive research exploration of ferrostatin-1 is
needed to ensure its safety and efficacy.
Elabela (ELA) is a novel endogenous ligand of the Apelin receptor (APJ)
that regulates oxidative stress and plays a protective role in
cardiovascular and cerebrovascular diseases. Zhang et
al89. found that ELA could significantly inhibit the
up-regulation of iron levels and lipid peroxidation in Ang II-induced
hypertensive mice. Further studies found that ELA inhibited cardiac
microvascular endothelial cell ferroptosis by regulating the
IL-6/STAT3/GPX4 signaling pathway. It has also been shown that ELA binds
to APJ and alleviates neuronal ferroptosis after ischemic stroke by
activating antioxidant signaling pathways99. The above
studies suggest that ELA inhibition of the ferroptosis pathway has a
certain potential in the treatment of hypertension and cardiovascular
and cerebrovascular diseases, which needs further clinical and basic
experiments to verify.