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Review
. 2024 Jan;19(1):6-13.
doi: 10.18502/jthc.v19i1.15531.

The Role of Leukemia Inhibitory Factor in Cardiovascular Disease: Signaling in Inflammation, Coagulation, and Angiogenesis

Hadi Rezaeeyan  1 , Bahareh Moghimian-Boroujeni  2 , Mehrnaz Abdolalian  3   1 , Mohammadreza Javan  4
Affiliations
Review

The Role of Leukemia Inhibitory Factor in Cardiovascular Disease: Signaling in Inflammation, Coagulation, and Angiogenesis

Hadi Rezaeeyan et al. J Tehran Heart Cent. 2024 Jan.

Abstract

Background: Cardiovascular disease (CVD) is one of the principal causes of mortality in the world. Various factors have been identified in the pathogenesis of CVD. Leukemia inhibitory factor (LIF) as a secretory cytokine is one of these factors. The LIF receptor is located on endothelial cells and plays a role in the expression of specific genes in these cells. Endothelial cells are the innermost cells of blood vessels, and defects in these cells cause endothelial dysfunction and eventually CVD.

Methods: The present study is based on PubMed database information (1982-2022) using the following words: "cardiovascular disease," "endothelial cells," "leukemia inhibitory factor," and "angiogenesis."

Results: LIF can cause arteriosclerotic plaques by activating inflammatory mechanisms in monocytes through the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. LIF can also induce vascular endothelial growth factor expression by activating signaling pathways, eventually leading to angiogenesis. Additionally, it can activate the coagulation cascade by factor VII production promotion within endothelial cells.

Conclusion: Understanding the interplay between LIF and the inflammation pathways, coagulation, and angiogenesis as key factors in CVD occurrence raises the possibility of targeting this factor as a potential strategy to mitigate CVD risk.

Keywords: Angiogenesis; Cardiovascular disease; Endothelial cells; Leukemia inhibitory factor.

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Figures

Figure 1
Figure 1
Leukemia inhibitory factor (LIF) can induce cardiovascular disease (CVD) by binding to the LIF receptor. The attachment induces angiogenic pathways, inflammation, and coagulation. LIF can stimulate vascular endothelial (VE)-cadherin expression by activating the signal transducer and activator of transcription (STAT) pathway and inducing Ras homolog family member A (RhoA protein). It affects CVD. This factor can also be mediated if vascular endothelial growth factor (VEGF), B-cell lymphoma-extra large (Bcl-xL), Wnt family member 5A (WnT5a), manganese superoxide dismutase (Mn-SOD), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and angiopoietin activate the angiogenesis mechanism, inducing angiogenesis in the heart muscle. The LIF factor can also affect the system by the following proteins: tissue factor, urokinase-type plasminogen activator (UPA), and fibrinogen.
See this image and copyright information in PMC

References

    1. Chistiakov DA, Shkurat TP, Melnichenko AA, Grechko AV, Orekhov AN. The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Ann Med 2018;50:121–127. - PubMed
    1. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee . Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation 2020;141:e139–e596. - PubMed
    1. Schwartz SM, Schwartz HT, Horvath S, Schadt E, Lee SI. A systematic approach to multifactorial cardiovascular disease: causal analysis. Arterioscler Thromb Vasc Biol 2012;32:2821–2835. - PubMed
    1. Zhao L, Varghese Z, Moorhead JF, Chen Y, Ruan XZ. CD36 and lipid metabolism in the evolution of atherosclerosis. Br Med Bull. 2018. Jun 1;126(1):101–112. - PubMed
    1. Khera AV, Kathiresan S. Genetics of coronary artery disease: discovery, biology and clinical translation. Nat Rev Genet 2017;18:331–344. - PMC - PubMed

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