3.1.3 Ferroptosis is involved in inducing plaque progression in
AS
Plaque rupture, intra-plaque bleeding, and thrombosis are also important
causes of AS progression. In the process of plaque formation in the late
stage of human carotid artery atherosclerosis, oxygen consumption in the
blood vessel wall increases and plaque lesions undergo hypoxia, which
stimulates angiogenesis and the resulting blood vessels are highly
permeable and brittle66. Moreover, advanced plaques
contain a large number of macrophages with pro-inflammatory phenotypes
that secrete stroma-degrading enzymes, leading to plaque instability,
plaque rupture, intra-plaque bleeding, and thrombotic
events67.
GPX4 is an important antioxidant and plays an anti-ferroptosis role in
the body. The severity of atherosclerosis was negatively correlated with
GPX4 expression68. Overexpression of GPX4 inhibits the
development of atherosclerosis by decreasing lipid peroxidation and
inhibiting the sensitivity of vascular cells to oxidized
lipids69. By up-regulating GPX4 expression and
enhancing GPX4 catalytic activity, vascular smooth muscle cell
proliferation can be inhibited and arterial protection can be
enhanced70. A single dose of selenium delivered to the
brain promotes the expression of the antioxidant GPX4, protects neurons,
and inhibits plaque growth in AS71. It was found that
Qing-Xin-Jie-Yu Granule partially inhibited ferroptosis in vulnerable AS
plaques through GPX4/ Xc- signaling pathway and weakened AS
progression72. Thus, upregulation of GPX4 expression
can slow plaque progression in AS by inhibiting ferroptosis.
Long non-coding RNAs (lncRNAs)
have been associated with atherosclerosis (AS), and lncRNA PVT1 was
found to be significantly upregulated in serum of patients with AS. In
vitro experiments using human vascular endothelial cells (HUVECs) showed
that knockdown of PVT1 and miR-106b-5p overexpression inhibited
increases in iron content, MDA levels, lipid ROS, ACSL4, and PTGS2, as
well as decreases in GSH and GPX4 in oxygen-LDL-induced HUVECs. The
study also found that PVT1 knockdown decreased lipid deposition,
atherosclerotic plaque number and size in ApoE mice. These results
suggest that PVT1 plays a key role in the progression of AS by
regulating the miR-106b-5p/ACSL4 axis in HUVECs, and therefore may be a
potential therapeutic target for AS73.