When iron levels are low, a protein called HIF1 becomes active in the walls of the aorta and is linked to higher levels of VEGF, a protein involved in changes to blood vessel structure and muscle...
Mechanism
Synthesis from 1 study
Without enough iron, the aorta acts like it's starved for oxygen, which turns on a signal that makes a protein called VEGF. That protein changes the muscle cells in the aorta from strong and tight to weak and messy, causing the wall to break down. This is the most likely way it happens based on...
Most probable mechanism
When the body lacks iron, it can't carry enough oxygen in the blood, so cells in the aorta act like they're not getting enough oxygen. This tricks a protein called HIF1 into staying active, which turns on another protein called VEGF. VEGF then causes the muscle cells in the aorta to change from being tight and strong to being loose and messy, which weakens the aorta wall and can lead to tearing.
Reduced iron availability impairs hemoglobin synthesis and oxygen delivery, creating a hypoxic environment in aortic tissue
Hypoxia and associated oxidative stress inhibit prolyl hydroxylase enzymes, preventing the degradation of HIF1α and allowing it to accumulate and translocate to the nucleus
Nuclear HIF1 dimerizes with HIF1β and binds to hypoxia-response elements in the promoter region of the VEGF gene, directly increasing VEGF transcription
Elevated VEGF signaling promotes the transition of vascular smooth muscle cells from a contractile state to a synthetic state, characterized by downregulation of contractile proteins and upregulation of matrix-degrading enzymes
Synthetic smooth muscle cells secrete matrix metalloproteinases that degrade elastic fibers and extracellular matrix, leading to structural weakening of the aortic wall
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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