LIM-only protein FHL2 attenuates vascular tissue factor activity, inhibits thrombus formation in mice and <i>FHL2</i> genetic variation associates with human venous thrombosis

Kroone, Chantal; Vos, Mariska; Rademakers, Timo; Kuijpers, Marijke J. E.; Hoogenboezem, Mark; Buul, Jaap D. van; Heemskerk, Johan W. M.; Ruf, Wolfram; Vlieg, Astrid van Hylckama; Versteeg, Henri H.; Goumans, Marie–José; Vries, Carlie J.M. de; Kurakula, Kondababu

doi:10.3324/haematol.2018.203026

Cited by 4 publications

(2 citation statements)

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“…Under physiological conditions, transmembrane glycoprotein TF is expressed at low levels in the pulmonary vessel wall, but its expression is significantly increased in pulmonary vascular lesions of PAH patients [ 61 , 62 , 63 ]. Increased TF/thrombin signaling contributes to vascular remodeling and the formation of plexiform lesions in PAH by inducing the proliferation and migration of SMCs and mediating the migration and angiogenesis of ECs.…”

Section: Factors Contributing To Ec Dysfunction In Phmentioning

confidence: 99%

Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

et al. 2021

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Pulmonary arterial hypertension (PAH) is a rare, complex, and progressive disease that is characterized by the abnormal remodeling of the pulmonary arteries that leads to right ventricular failure and death. Although our understanding of the causes for abnormal vascular remodeling in PAH is limited, accumulating evidence indicates that endothelial cell (EC) dysfunction is one of the first triggers initiating this process. EC dysfunction leads to the activation of several cellular signalling pathways in the endothelium, resulting in the uncontrolled proliferation of ECs, pulmonary artery smooth muscle cells, and fibroblasts, and eventually leads to vascular remodelling and the occlusion of the pulmonary blood vessels. Other factors that are related to EC dysfunction in PAH are an increase in endothelial to mesenchymal transition, inflammation, apoptosis, and thrombus formation. In this review, we outline the latest advances on the role of EC dysfunction in PAH and other forms of pulmonary hypertension. We also elaborate on the molecular signals that orchestrate EC dysfunction in PAH. Understanding the role and mechanisms of EC dysfunction will unravel the therapeutic potential of targeting this process in PAH.

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Section: Factors Contributing To Ec Dysfunction In Phmentioning

confidence: 99%

Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

et al. 2021

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“…FHL2 interacts with Tissue Factor resulting in a reduction of its coagulation activity, and there is thus enhanced blood clot formation in FHL2-deficient mice. Furthermore, FHL2 SNP rs4851770 was shown to associate with the risk of developing venous thrombosis in humans [59]. Given the specific location of this SNP, it has been classified as an upstream transcript variant that forms part of intron 1 in two FHL2 transcript variants, but not in others.…”

Section: Fhl2 Snps In Coagulation and Cancermentioning

confidence: 99%

How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

Habibe

Clemente-Olivo

Vries

2021

Cells

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Susceptibility to complex pathological conditions such as obesity, type 2 diabetes and cardiovascular disease is highly variable among individuals and arises from specific changes in gene expression in combination with external factors. The regulation of gene expression is determined by genetic variation (SNPs) and epigenetic marks that are influenced by environmental factors. Aging is a major risk factor for many multifactorial diseases and is increasingly associated with changes in DNA methylation, leading to differences in gene expression. Four and a half LIM domains 2 (FHL2) is a key regulator of intracellular signal transduction pathways and the FHL2 gene is consistently found as one of the top hyper-methylated genes upon aging. Remarkably, FHL2 expression increases with methylation. This was demonstrated in relevant metabolic tissues: white adipose tissue, pancreatic β-cells, and skeletal muscle. In this review, we provide an overview of the current knowledge on regulation of FHL2 by genetic variation and epigenetic DNA modification, and the potential consequences for age-related complex multifactorial diseases.

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Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532

Gao

et al. 2022

Annals of Vascular Surgery

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LIM-only protein FHL2 attenuates vascular tissue factor activity, inhibits thrombus formation in mice and FHL2 genetic variation associates with human venous thrombosis

Cited by 4 publications

References 48 publications

Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease

Metformin Inhibits Multiple Myeloma Serum-induced Endothelial Cell Thrombosis by Down-Regulating miR-532

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