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Review
. 2024 Dec 12;14(12):1592.
doi: 10.3390/biom14121592.

The Physiological Functions and Therapeutic Potential of Hypoxia-Inducible Factor-1α in Vascular Calcification

Zhenghong Zhang  1 , Defan Wang  2 , Renfeng Xu  1 , Xiang Li  3 , Zhengchao Wang  1   3 , Yang Zhang  3
Affiliations
Review

The Physiological Functions and Therapeutic Potential of Hypoxia-Inducible Factor-1α in Vascular Calcification

Zhenghong Zhang et al. Biomolecules. .

Abstract

HIF-1α plays a crucial regulatory role in vascular calcification (VC), primarily influencing the osteogenic differentiation of VSMCs through oxygen-sensing mechanisms. Under hypoxic conditions, the stability of HIF-1α increases, avoiding PHD and VHL protein-mediated degradation, which promotes its accumulation in cells and then activates gene expressions related to calcification. Additionally, HIF-1α modulates the metabolic state of VSMCs by regulating the pathways that govern the switch between glycolysis and oxidative phosphorylation, thereby further advancing the calcification process. The interaction between HIF-1α and other signaling pathways, such as nuclear factor-κB, Notch, and Wnt/β-catenin, creates a complex regulatory network that serves as a critical driving force in VC. Therefore, a deeper understanding of the role and regulatory mechanism of the HIF-1α signaling during the development and progression of VC is of great significance, as it is not only a key molecular marker for understanding the pathological mechanisms of VC but also represents a promising target for future anti-calcification therapies.

Keywords: energy metabolism; hypoxia-inducible factor-1α; therapeutic target; vascular calcification; vascular smooth muscle cell.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
HIF-1α metabolism under normoxic and hypoxic conditions. VHL: the Von Hippel–Lindau ubiquitin-E3 ligase complex.
Figure 2
Figure 2
Role of HIF-1α in ROS-triggered osteochondrogenic transdifferentiation of VSMC during vascular calcification.
Figure 3
Figure 3
The effect of HIF-1α on VSMC transdifferentiation.
Figure 4
Figure 4
The regulation of HIF-1α on calcification-related factors in VSMCs.
Figure 5
Figure 5
The interaction between HIF-1α and inflammation in vascular calcification.
Figure 6
Figure 6
The oxygen-sensing mechanism of HIF-1α regulating vascular calcification.
Figure 7
Figure 7
The regulation of metabolic pathways by HIF-1α.
Figure 8
Figure 8
The interaction between HIF-1α and other pathways during the occurrence and progression of vascular calcification.
Figure 9
Figure 9
The potential therapeutic target of HIF-1α in vascular calcification.
See this image and copyright information in PMC

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References

    1. Zhu D., Mackenzie N.C., Farquharson C., Macrae V.E. Mechanisms and clinical consequences of vascular calcification. Front. Endocrinol. 2012;3:95. doi: 10.3389/fendo.2012.00095. - DOI - PMC - PubMed
    1. Liberman M., Pesaro A.E., Carmo L.S., Serrano C.V., Jr. Vascular calcification: Pathophysiology and clinical implications. Einstein. 2013;11:376–382. doi: 10.1590/S1679-45082013000300021. - DOI - PMC - PubMed
    1. Copur S., Ucku D., Cozzolino M., Kanbay M. Hypoxia-inducible factor signaling in vascular calcification in chronic kidney disease patients. J. Nephrol. 2022;35:2205–2213. doi: 10.1007/s40620-022-01432-8. - DOI - PubMed
    1. Davies M.R., Hruska K.A. Pathophysiological mechanisms of vascular calcification in end-stage renal disease. Kidney Int. 2001;60:472–479. doi: 10.1046/j.1523-1755.2001.060002472.x. - DOI - PubMed
    1. Dube P., DeRiso A., Patel M., Battepati D., Khatib-Shahidi B., Sharma H., Gupta R., Malhotra D., Dworkin L., Haller S., et al. Vascular calcification in chronic kidney disease: Diversity in the vessel wall. Biomedicines. 2021;9:404. doi: 10.3390/biomedicines9040404. - DOI - PMC - PubMed

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