Potential Contributions of Intimal and Plaque Hypoxia to Atherosclerosis

Fong, Guo‐Hua

doi:10.1007/s11883-015-0510-0

Cited by 35 publications

(18 citation statements)

References 86 publications

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“…The proliferation, migration, and differentiation of VSMCs is involved in atherosclerotic plaque progression, and dysfunctional VSMCs accelerate AS progression [22,26]. When stimulated by a dysfunctional endothelium and inflammatory factors, VSMCs differentiate and proliferate, and form a fibrous cap [17]. Here, we provide evidence that ox-LDLs induced the expression of CXCL12 in PMA-stimulated THP-1 cells and HA-VSMCs.…”

Section: Discussionmentioning

confidence: 63%

Foam cells promote atherosclerosis progression by releasing CXCL12

Rong

et al. 2020

Bioscience Reports

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Background: Atherosclerosis (AS) is a chronic inflammatory disease that contributes to multiple cardiovascular diseases (CVDs), and foam cell formation plays important roles in the progression of AS. There is an urgent need to identify new molecular targets for treating AS, and thereby improve the quality of life and reduce the financial burden of individuals with CVD. Methods: An in vitro model of AS was generated by treating THP-1 cells and human aortic vascular smooth muscle cells (HA-VSMCs) with oxidized low-density lipoproteins (ox-LDLs). HA-VSMC proliferation and foam cell formation were detected by the MTT assay and Oil Red O staining. C–X–C motif chemokine 12 (CXCL12) expression was suppressed by siRNA. An AS rat model was established by feeding rats a high-fat diet and vitamin D2 for 3 weeks. Histopathology examinations were conducted by Hematoxylin and Eosin (H&E) staining and the levels ionized calcium-binding adapter molecule 1 (IBA1) and α smooth muscle actin (α-SMA) expression were determined by ELISA assays and immunohistochemistry. Results: An in vitro model of AS was established with THP-1 cells. CXCL12 expression in the model THP-1 cells was significantly increased when compared with its expression in control cells. Suppression of CXCL12 expression reduced the progression of AS in the cell model. Moreover, CXCL12 promoted AS in the in vivo rat model. Conclusion: Our results suggest that CXCL12 plays an important role in promoting the progression of AS. Furthermore, inhibition of CXCL12 might suppress the development of AS by inhibiting HA-VSMC proliferation and their transformation to foam cells.

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Section: Discussionmentioning

confidence: 63%

Foam cells promote atherosclerosis progression by releasing CXCL12

Rong

et al. 2020

Bioscience Reports

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“…Pathways we found significantly differentially expressed consist mostly of inflammatory pathways with some hypoxia related signaling as well. We consider the differentially expressed hypoxia induced signaling pathways 47 , together with the differential expression of HOX genes 26 , to show that the processes necessary for the formation of neovessels and repair of the vascular wall are active in the aneurysmatic aorta 48 . Other pathways, that are differentially expressed, are likely to be a result of leukocyte-activity at the aortic site.…”

Section: Discussionmentioning

confidence: 99%

Differentially expressed genes and canonical pathways in the ascending thoracic aortic aneurysm – The Tampere Vascular Study

Sulkava

Raitoharju

Mennander

et al. 2017

Sci Rep

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Ascending thoracic aortic aneurysm (ATAA) is a multifactorial disease with a strong inflammatory component. Surgery is often required to prevent aortic rupture and dissection. We performed gene expression analysis (Illumina HumanHT-12 version 3 Expression BeadChip) for 32 samples from ATAA (26 without/6 with dissection), and 28 left internal thoracic arteries (controls) collected in Tampere Vascular study. We compared expression profiles and conducted pathway analysis using Ingenuity Pathway Analysis (IPA) to reveal differences between ATAA and a healthy artery wall. Almost 5000 genes were differentially expressed in ATAA samples compared to controls. The most downregulated gene was homeobox (HOX) A5 (fold change, FC = −25.3) and upregulated cadherin-2 (FC = 12.6). Several other HOX genes were also found downregulated (FCs between -25.3 and -1.5, FDR < 0.05). 43, mostly inflammatory, canonical pathways in ATAA were found to be significantly (p < 0.05, FDR < 0.05) differentially expressed. The results remained essentially the same when the 6 dissected ATAA samples were excluded from the analysis. We show for the first time on genome level that ATAA is an inflammatory process, revealing a more detailed molecular pathway level pathogenesis. We propose HOX genes as potentially important players in maintaining aortic integrity, altered expression of which might be important in the pathobiology of ATAA.

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“…7,18 Among the resulting gene products, vascular endothelial growth factor (VEGF) is among the most relevant to angiogenesis. 3,11 Current research suggests that hypoxia promotes plaque growth by stimulating angiogenesis, monocyte infiltration, and oxidized low-density lipoprotein uptake into macrophages, 6 and we also know that HIF-1a and VEGF accumulate in symptomatic or histologically unstable lesions. 9,20 However, we do not presently understand the role of plaque hypoxia before carotid endarterectomy (CEA) and carotid artery stenting (CAS).…”

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confidence: 99%

Carotid artery stenosis with a high-intensity signal plaque on time-of-flight magnetic resonance angiography and association with evidence of intraplaque hypoxia

Ogata¹,

Kawashima²,

Wakamiya³

et al. 2016

JNS

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OBJECTIVE Hypoxia induces angiogenesis and plays a major role in the progression of carotid plaques. During carotid intervention, plaques with high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) often cause ischemic stroke and embolic complications. However, the role of intraplaque hypoxia before carotid endarterectomy (CEA) and carotid artery stenting is not presently understood. In this study the authors aimed to investigate the relationship between intraplaque hypoxia and MRA findings. METHODS Nineteen consecutive patients with 20 carotid artery stenoses who underwent CEA at Saga University Hospital between August 2008 and December 2014 were enrolled in the study. The expressions of hypoxia-inducible transcription factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemical analysis. In addition, the relationship between the findings on TOF MRA and pathology for the carotid plaques was analyzed. RESULTS High-intensity plaques on TOF MRA showed higher expression levels of HIF-1α (p = 0.015) and VEGF (p = 0.007) compared with isointensity plaques. The rate of intraplaque hemorrhage (IPH) on TOF MRA was also significantly higher in the high-intensity plaques than in the isointensity plaques (p = 0.024). Finally, the mean number of neovessels was significantly higher in those without plaque hemorrhage than in those with plaque hemorrhage (p = 0.010). CONCLUSIONS Plaques with high-intensity signals on TOF MRA were associated with IPH and evidence of intraplaque hypoxia. This fact may represent an opportunity to establish novel therapeutic agents targeting intraplaque hypoxia.

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Potential Contributions of Intimal and Plaque Hypoxia to Atherosclerosis

Cited by 35 publications

References 86 publications

Foam cells promote atherosclerosis progression by releasing CXCL12

Foam cells promote atherosclerosis progression by releasing CXCL12

Differentially expressed genes and canonical pathways in the ascending thoracic aortic aneurysm – The Tampere Vascular Study

Carotid artery stenosis with a high-intensity signal plaque on time-of-flight magnetic resonance angiography and association with evidence of intraplaque hypoxia

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