Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis

Huang, Qingyan; Gan, Yuhong; Yu, Zhikang; Wu, Heming; Zhong, Zhixiong

doi:10.3389/fcvm.2021.734550

Cited by 31 publications

(29 citation statements)

References 96 publications

(87 reference statements)

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“…Second, the experimental design followed in those studies was different, relying on a triggering stimulus, such as periostin, TGF-beta, or hypoxia, to study the signaling pathways involved, while our study shows the effect of a decrease in ILK levels [ 43 , 46 , 47 , 48 ]. Third, ILK expression in the cardiovascular system is mainly cardioprotective, as explained above; thus, a slight reduction in its expression levels results in dramatic pathological changes, EndMT being one process involved in cardiovascular pathologies [ 49 ]. Thus, although additional studies will be necessary to dissect the molecular pathways involved in the transdifferentiation program initiated by ILK depletion, our study is the first to show the involvement of ILK in EndMT in the setting of CAVD development.…”

Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease

et al. 2022

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Calcific aortic valve disease (CAVD) is highly prevalent during aging. CAVD initiates with endothelial dysfunction, leading to lipid accumulation, inflammation, and osteogenic transformation. Integrin-linked kinase (ILK) participates in the progression of cardiovascular diseases, such as endothelial dysfunction and atherosclerosis. However, ILK role in CAVD is unknown. First, we determined that ILK expression is downregulated in aortic valves from patients with CAVD compared to non-CAVD, especially at the valve endothelium, and negatively correlated with calcification markers. Silencing ILK expression in human valve endothelial cells (siILK-hVECs) induced endothelial-to-mesenchymal transition (EndMT) and promoted a switch to an osteoblastic phenotype; SiILK-hVECs expressed increased RUNX2 and developed calcified nodules. siILK-hVECs exhibited decreased NO production and increased nitrosative stress, suggesting valvular endothelial dysfunction. NO treatment of siILK-hVECs prevented VEC transdifferentiation, while treatment with an eNOS inhibitor mimicked ILK-silencing induction of EndMT. Accordingly, NO treatment inhibited VEC calcification. Mechanistically, siILK-hVECs showed increased Smad2 phosphorylation, suggesting a TFG-β-dependent mechanism, and NO treatment decreased Smad2 activation and RUNX2. Experiments performed in eNOS KO mice confirmed the involvement of the ILK-eNOS signaling pathway in valve calcification, since aortic valves from these animals showed decreased ILK expression, increased RUNX2, and calcification. Our study demonstrated that ILK endothelial expression participates in human CAVD development by preventing endothelial osteogenic transformation.

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Section: Discussionmentioning

confidence: 99%

Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease

et al. 2022

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“…Endothelial-mesenchymal transition (EndMT) is a process of cell differentiation in which endothelial cells acquire mesenchymal properties. EndMT is associated with the development of atherosclerosis and can cause a number of phenotypic changes in endothelial cells, including their dysfunction as well as plaque formation [ 170 ]. Unidirectional laminar flow protects endothelial cells from EndMT, whereas impaired flow promotes EndMT formation.…”

Section: Role Of Klf2 and Klf4 In Cross-links Of Cellular Immunometab...mentioning

confidence: 99%

Participation of Krüppel-like Factors in Atherogenesis

Kotlyarov

Kotlyarova

2023

Metabolites

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Atherosclerosis is an important problem in modern medicine, the keys to understanding many aspects of which are still not available to clinicians. Atherosclerosis develops as a result of a complex chain of events in which many cells of the vascular wall and peripheral blood flow are involved. Endothelial cells, which line the vascular wall in a monolayer, play an important role in vascular biology. A growing body of evidence strengthens the understanding of the multifaceted functions of endothelial cells, which not only organize the barrier between blood flow and tissues but also act as regulators of hemodynamics and play an important role in regulating the function of other cells in the vascular wall. Krüppel-like factors (KLFs) perform several biological functions in various cells of the vascular wall. The large family of KLFs in humans includes 18 members, among which KLF2 and KLF4 are at the crossroads between endothelial cell mechanobiology and immunometabolism, which play important roles in both the normal vascular wall and atherosclerosis.

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“…Following the rationale of relating atheroma biology with clinical approaches, it might also be tempting to specifically target activated endothelial cells in order to reverse the endMT process ( Zhang et al, 2021b ; Huang et al, 2021 ), or specifically focus on inhibiting the dedifferentiation of vascular SMC by promoting the recovery of their contractile phenotype ( Shi et al, 2021 ). Another potential therapeutic strategy could be the enhancing of efferocytosis, the removal of unwanted/pathogenic plaque-associated cells by own phagocytes, in order to induce plaque regression.…”

Section: Inflammation Leads To Atheroma Formation and Tumour Cell Mas...mentioning

confidence: 99%

Clinical implications of inflammation in atheroma formation and novel therapies in cardiovascular diseases

Barungi

Hernández-Camarero²,

Moreno-Terribas³

et al. 2023

Front. Cell Dev. Biol.

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Cardiovascular diseases (CVD) are the leading causes of death and disability in the world. Among all CVD, the most common is coronary artery disease (CAD). CAD results from the complications promoted by atherosclerosis, which is characterized by the accumulation of atherosclerotic plaques that limit and block the blood flow of the arteries involved in heart oxygenation. Atherosclerotic disease is usually treated by stents implantation and angioplasty, but these surgical interventions also favour thrombosis and restenosis which often lead to device failure. Hence, efficient and long-lasting therapeutic options that are easily accessible to patients are in high demand. Advanced technologies including nanotechnology or vascular tissue engineering may provide promising solutions for CVD. Moreover, advances in the understanding of the biological processes underlying atherosclerosis can lead to a significant improvement in the management of CVD and even to the development of novel efficient drugs. To note, over the last years, the observation that inflammation leads to atherosclerosis has gained interest providing a link between atheroma formation and oncogenesis. Here, we have focused on the description of the available therapy for atherosclerosis, including surgical treatment and experimental treatment, the mechanisms of atheroma formation, and possible novel therapeutic candidates such as the use of anti-inflammatory treatments to reduce CVD.

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Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis

Cited by 31 publications

References 96 publications

Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease

Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease

Participation of Krüppel-like Factors in Atherogenesis

Clinical implications of inflammation in atheroma formation and novel therapies in cardiovascular diseases

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