Topographic patterns of vascular disease: HOX proteins as determining factors?

Visconti, Richard P.; Awgulewitsch, Alexander

doi:10.4331/wjbc.v6.i3.65

Cited by 12 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TEA‐derived cells overexpressed specific HOX ‐class genes, such as HOXC9 (Figure S4C ), which is known to play a role in the development and rostrocaudal gene expression patterns. 24 These findings resonate with findings in dogs, where transcription patterns of vascular cells were dependent on vessel localization. 25 Moreover, the enrichment analysis showed ongoing pathways related to neutrophils in CEA (Figure S4D ).…”

Section: Resultssupporting

confidence: 82%

Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis

Buono,

Benavente,

Slenders

et al. 2023

JAHA

View full text Add to dashboard Cite

Background Plaque myofibroblasts are critical players in the initiation and advancement of atherosclerotic disease. They are involved in the production of extracellular matrix, the formation of the fibrous cap, and the underlying lipidic core via modulation processes in response to different environmental cues. Despite clear phenotypic differences between myofibroblast cells and healthy vascular smooth muscle cells, smooth muscle cells are still widely used as a cellular model in atherosclerotic research. Methods and Results Here, we present a conditioned outgrowth method to isolate and culture myofibroblast cells from plaques. We obtained these cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that they keep their proliferative capacity for 8 passages, are transcriptionally stable, retain donor‐specific gene expression programs, and express extracellular matrix proteins ( FN1 , COL1A1 , and DCN ) and smooth muscle cell markers ( ACTA2 , MYH11 , and CNN1 ). Single‐cell transcriptomics reveals that the cells in culture closely resemble the plaque myofibroblasts. Chromatin immunoprecipitation sequencing shows the presence of histone H3 lysine 4 dimethylation at the MYH11 promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque myofibroblasts can be efficiently transduced (>97%) and are capable of taking up oxidized low‐density lipoprotein and undergoing calcification. Conclusions In conclusion, we present a method to isolate and culture cells that retain plaque myofibroblast phenotypical and functional capabilities, making them a suitable in vitro model for studying selected mechanisms of atherosclerosis.

show abstract

Section: Resultssupporting

confidence: 82%

Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis

Buono,

Benavente,

Slenders

et al. 2023

JAHA

View full text Add to dashboard Cite

show abstract

“…The TEA-derived cells overexpressed specific HOX-class genes such as HOXC9 (Fig. S2 B), which is known for playing a role in the development and rostro-caudal gene expression patterns (17). These findings resonate with findings in dogs where transcription patterns of vascular cells were dependent on vessel localization (18).…”

Section: Resultsmentioning

confidence: 99%

Human primary plaque cell cultures to study mechanisms of atherosclerosis

Buono

Benavente

Slenders

et al. 2023

Preprint

View full text Add to dashboard Cite

Plaque smooth muscle cells are critical players in the initiation and advancement of atherosclerotic disease. They produce extracellular matrix (ECM) components, which play a role in lesion progression and stabilization. Despite clear phenotypic differences between plaque smooth muscle cells and vascular smooth muscle cells (VSMCs), VSMCs are still widely used as a model system in atherosclerotic research. Here we present a conditioned outgrowth method to isolate plaque smooth muscle cells. We obtained plaque cells from 27 donors (24 carotid and 3 femoral endarterectomies). We show that these cells keep their proliferative capacity for eight passages, are transcriptionally stable, retain donor-specific gene expression programs, and express extracellular matrix proteins (FN1, COL1A1, DCN) and smooth muscle cell markers (ACTA2, MYH11, CNN1). Single-cell transcriptomics of plaque tissue and cultured cells reveals that cultured plaque cells closely resemble the myofibroblast fraction of plaque smooth muscle cells. Chromatin immunoprecipitation sequencing (ChIP-seq) shows the presence of histone H3 lysine 4 dimethylation (H3K4me2) at the MYH11 promoter, pointing to their smooth muscle cell origin. Finally, we demonstrated that plaque cells can be efficiently transduced (>97%) and are capable to take up oxidized LDL (oxLDL) and undergo calcification. In conclusion, we present a method to isolate and culture primary human plaque cells that retain plaque myofibroblast-like cells' phenotypical and functional capabilities - making them a suitable in vitro model for studying selected mechanisms of atherosclerosis.

show abstract

“…HoxA5 is endothelial function regulator and is involved in migration, inflammation and angiogenesis. CAMP response elements (CRE) in relation with HoxA5, Klf3, Cmklr 1, Acvrk1, spry2 and other genes, serves as mechanosensitive master switch in gene expression [ 81 ]. Cells in vascular bed are quiescent and in vascular beds there resides niche for stem cells.…”

Section: Resultsmentioning

confidence: 99%

Switching of vascular cells towards atherogenesis, and other factors contributing to atherosclerosis: a systematic review

Shafi

2020

Thrombosis J

View full text Add to dashboard Cite

Background Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing. Methods Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells. Results Atherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET – 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl − 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others. This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis. Conclusion The development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity. The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in ‘switching’ of vascular cells towards atherosclerosis.

show abstract

Topographic patterns of vascular disease: HOX proteins as determining factors?

Cited by 12 publications

References 30 publications

Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis

Human Plaque Myofibroblasts to Study Mechanisms of Atherosclerosis

Human primary plaque cell cultures to study mechanisms of atherosclerosis

Switching of vascular cells towards atherogenesis, and other factors contributing to atherosclerosis: a systematic review

Contact Info

Product

Resources

About