Low iron levels in the body are linked to higher levels of oxidative damage in the aorta and increased activity of the HIF1 protein, which may be a result of that oxidative damage.
Mechanism
Synthesis from 1 study
Not enough iron means less oxygen gets to the aorta, which causes harmful molecules to build up and damage DNA. These molecules also stop the body from breaking down a protein called HIF1, so it accumulates and triggers changes in aortic cells that weaken the blood vessel wall. The same harmful...
Most probable mechanism
When there isn't enough iron in the body, blood can't carry oxygen well, so tissues like the aorta get less oxygen. This lack of oxygen, along with a buildup of harmful molecules called reactive oxygen species, stops enzymes that normally break down a protein called HIF1. As a result, HIF1 builds up and turns on genes that make cells in the aorta change their behavior, leading to damage and weakening of the aortic wall. The buildup of reactive oxygen species also directly damages DNA in the aorta, leaving a marker called 8-OHdg.
Iron deficiency reduces hemoglobin synthesis and oxygen-carrying capacity of blood, leading to diminished oxygen delivery to aortic tissue
Reduced oxygen availability and increased mitochondrial electron leakage elevate reactive oxygen species in aortic cells, causing oxidative DNA damage measured as 8-OHdg
Elevated reactive oxygen species and low oxygen inhibit prolyl hydroxylase enzymes, preventing hydroxylation and proteasomal degradation of HIF1α
Stabilized HIF1α translocates to the nucleus, dimerizes with HIF1β, and activates transcription of hypoxia-responsive genes including VEGF
HIF1-driven gene expression promotes phenotypic switching of vascular smooth muscle cells from contractile to synthetic states, increasing matrix metalloproteinase secretion and extracellular matrix degradation
Evidence from Studies
Supporting (1)
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Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection
Contradicting (0)
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