Abstract: P246 CCN3 INHIBITS NEOINTIMAL HYPERPLASIA THROUGH MODULATION OF SMOOTH MUSCLE CELL GROWTH AND MIGRATION

Shimoyama, Tatsushi; Hiraoka, Shûichi; Takemoto, Minoru; Saitō, Yasushi; Koseki, Haruhiko; Yokote, Kotaro

doi:10.1016/s1567-5688(09)70541-0

Cited by 2 publications

(3 citation statements)

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“…Top differentially expressed genes within the ascending SMC population includes expected developmental genes such as Tbx20 and Hand2 , but also numerous genes with previously demonstrated roles in atherosclerosis suggesting vascular bed specific disease risk mechanisms (Figure 2I, Supplemental Table 2). These genes include Ccn3 (cellular communication network factor 3) which has previously reported vascular protective effects by inhibiting neointimal formation and plaque development; 34, 35 Dcn (decorin), which has been shown to be protective in atherosclerosis; 36 Col14a1 (collagen type XIV alpha 1 chain) which has increased expression in human atherosclerotic plaque; 37 and Tns1 (tensin 1) a previously identified CAD GWAS gene. 38 Notably, we identify specific vascular development and inflammation genes as having higher expression within SMCs isolated from the carotid artery, such as Junb (junb proto-oncogene) (Figure 2J, Supplemental Table 3), Atf3 (activating transcription factor 3), and Egr1 (early growth response 1).…”

Section: Resultsmentioning

confidence: 99%

“…Prior experimental work has shown that Ccn3 inhibits neointima formation through inhibition of vascular smooth muscle proliferation and regulation of macrophage foam cell formation, while overexpression of Ccn3 inhibits vascular inflammation and is protective against atherosclerosis in mice. 34, 35, 85 Given the differential expression of Ccn3 between vascular beds, one hypothesis may be that this Ccn3 pathway plays differing roles in mediating disease across vascular beds. Perhaps this suggests that augmenting this pathway may prove to have a greater benefit in vascular beds which are ‘deficient’ in Ccn3 , i.e.…”

Section: Discussionmentioning

confidence: 99%

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The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci

Weldy

Cheng

Pedroza³

et al. 2022

Preprint

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Rationale: Vascular beds have distinct susceptibility to atherosclerosis and aneurysm, yet the biological underpinnings of vascular bed specific disease risk are largely unknown. Vascular tissues have different developmental origins which may influence global chromatin accessibility. Understanding chromatin accessibility and gene expression profiles on single cell resolution is crucial to gain insight into vascular bed specific disease risk. Objective: We aim to understand, on single cell resolution, the global chromatin accessibility and gene expression profiles across distinct vascular beds in the healthy adult mouse to provide insight into the potential mechanisms of vascular bed specific disease risk. Methods and Results: We performed single cell chromatin accessibility (scATACseq) and gene expression profiling (scRNAseq) of healthy adult mouse vascular tissue from three vascular beds, 1) aortic root and ascending aorta, 2) brachiocephalic and carotid artery, and 3) descending thoracic aorta. By integrating datasets and comparing vascular beds within cell type, we identified thousands of differentially accessible chromatin peaks within smooth muscle cells, fibroblasts, and endothelial cells, demonstrating numerous enhancers to be vascular bed specific. We revealed an epigenetic memory of embryonic origin with differential chromatin accessibility of key developmental transcription factors such as Tbx20, Hand2, Gata4, and Hoxb family. Differentially accessible chromatin regions within cell type are also heavily weighted towards genes with known roles in mediating vascular disease risk. Furthermore, cell type specific transcription factor motif accessibility varies by vascular bed, all of which suggest epigenomic profiles as having specific roles in vascular bed specific disease risk. Conclusions: This work supports a paradigm that the epigenomic landscapes of vascular cells are cell type and vascular bed specific and that differentially accessible regions are heavily weighted towards disease risk genes. This work gives insight into vascular bed specific transcriptional and epigenetic programs and highlights the potential for vascular bed specific mechanisms of disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci

Weldy

Cheng

Pedroza³

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…CCN3 is involved in myogenesis, affecting the formation and stabilization of attachment structures that transmit force from the muscle to tendon (Lafont et al, 2005). In contrast, Ccn3-deficient mice develop normally until adulthood and both males and females can reproduce (Shimoyama et al, 2010). Similarly, Ccn3 mutant mice deficient in the VWC domain displayed good health, albeit with mild skeletal defects (Heath et al, 2008).…”

Section: The Expression Pattern Of Ccn2 During Development Ismentioning

confidence: 99%

Emerging Mechanisms of Cyr61/CTGF/NOV Secretion in the Nervous System

2022

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The Cyr61/CTGF/NOV (CCN) family is dynamically expressed in various tissues, including the nervous system, from the prenatal period to adulthood. However, major studies have been conducted only in limited fields, such as the cardiovascular and muscular systems, skeletal development, and cancer. In addition, although the CCN family is a secretory protein, very few studies have described its mechanism of secretion. Recently, it has been suggested that overexpression of CCN3 or intracellular accumulation due to problems in the secretory pathway can inhibit neuronal axonal growth. In this review, we have briefly summarized the structure and characteristics of the CCN family and its related diseases, with particular emphasis on the secretory mechanism and modifiers of the CCN family, newly identified in the nervous system.

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Abstract: P246 CCN3 INHIBITS NEOINTIMAL HYPERPLASIA THROUGH MODULATION OF SMOOTH MUSCLE CELL GROWTH AND MIGRATION

Cited by 2 publications

References 0 publications

The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci

The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci

Emerging Mechanisms of Cyr61/CTGF/NOV Secretion in the Nervous System

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