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

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.

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.