The arterial microenvironment: the where and why of atherosclerosis

Yurdagul, Arif; Finney, Alexandra C; Woolard, Matthew D.; Orr, A. Wayne

doi:10.1042/bj20150844

Cited by 146 publications

(118 citation statements)

References 186 publications

(256 reference statements)

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“…The early atherosclerotic lesions are characterized by the accumulation of arte-DOI: 10.1159/000495037 rial foam cells derived mainly from cholesterol-loaded macrophages [2,3] and therefore, clinical interest has focused on lipid parameters such as total cholesterol (TCh), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), TCh-HDL ratio, triglycerides (TG) [4,5]. Moreover, the dysfunction of cells in the bloodstream (leukocytes and platelets) induces the secretion of pro-inflammatory cytokines [6,7].…”

Section: Introductionmentioning

confidence: 99%

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

et al. 2018

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Background: L-carnitine can be metabolized to trimethylamine N-oxide (TMAO), a molecule that promotes atherogenesis through its interaction with macrophages and lipid metabolism. Objective: The aim of the present study was to assess whether L-carnitine supplementation may promote changes in selected serum biomarkers of atherosclerosis. Methods: Before the start, in the mid-point and after completing the 24-weeks supplementation protocol, fasting blood samples were taken from the antecubital vein. Plasma free L-carnitine and TMAO were determined by the UPLC/MS/MS method. Serum proteins were determined by the enzyme immunoassay method using commercially available kits. Total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides have been determined using standard automatic analyzer. Results: L-carnitine supplementation elevated fasting plasma carnitine in the mid-point of our study and it remained increased until the end of supplementation period. Moreover, it induced tenfold increase in plasma TMAO concentration but did not affect serum C-reactive protein, interleukin-6, tumour necrosis factor-α, L-selectin, P-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 or lipid profile markers. Conclusion: We demonstrated that although oral L-carnitine supplementation significantly increased plasma TMAO concentration, no lipid profile changes or other markers of adverse cardiovascular events were detected in healthy aged women over the period of 24 weeks.

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Section: Introductionmentioning

confidence: 99%

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

et al. 2018

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“…VCAM-1, ICAM-1, P-selectin, and PECAM-1) and proinflammatory cytokines [42,43], impaired the endothelial permeability, and facilitated the recruitment and infiltration of inflammatory cell [40]. The inflammatory monocytes further differentiate and proliferate into macrophages that ingest the oxidized low-density lipoprotein forming foam cells.…”

Section: Dual Effects Of Shear Stress On Atherosclerosismentioning

confidence: 99%

“…Thus, dysfunctional endothelium in the atherosclerosis-susceptible location is an early manifestation of atherosclerosis [40].…”

Section: Dual Effects Of Shear Stress On Atherosclerosismentioning

confidence: 99%

Endothelial Glycocalyx: Novel Insight into Atherosclerosis

Zeng¹

2017

J. Biomed

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The evidence shows that endothelial glycocalyx exerts an important role in inflammation and atherosclerosis. We previously demonstrated that hydrodynamic force such as shear stress induces the remodeling of the major component of glycocalyx including glypican-1 with attached heparan sulfate, and that sphingosine-1-phosphate (S1P) protects the glycocalyx against syndecan-1 ectodomain shedding and induces the synthesis of HS. Actually, both shear stress and S1P imposed significant influence on inflammatory disease such as atherosclerosis. Therefore, it can be concluded that glycocalyx is a critical signaling platform for determining the fate of endothelial cells and atherosclerosis. This review integrated our current understanding of shear stress, S1P and glycocalyx, and also provided new insight/issues into the role of the glycocalyx in the process of forming and developing atherosclerosis.

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“…In the human data in Figure 10 in 174 . Fibronectin has been shown to promote SMC proliferation and signal through integrin V beta 3 (α V β 3 ) 55,127 .…”

Section: Is There An Alternative Cell Source Of Col15a1 Within Lesions?mentioning

confidence: 99%

“…TGFβ, IL1β, and oxidized phospholipids) [11][12][13] and that collagens can influence SMC migration, proliferation, and adhesion 13,127 . However, definitive evidence for SMC as the in vivo source of collagen within lesions is lacking as: 1) collagen subtypes are secreted molecules making it difficult to ascertain their cell source;…”

Section: Introductionmentioning

confidence: 99%

"Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions"

Durgin

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Atherosclerotic plaque rupture or erosion with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke [1][2][3][4][5][6] . Plaque stability is classically characterized by a fibrous cap rich in ACTA2 + presumed smooth muscle cells (SMC) and collagen with a paucity of CD68 + presumed macrophages [7][8][9][10] . The dogma in the field is that SMC produce collagens that in turn provide tensile strength and stability to atherosclerotic plaques. This has largely been supported by evidence that SMC can produce collagens in vitro [11][12][13] . However, there is no direct evidence in vivo that SMC produce collagens as: 1) collagens are secreted molecules making it challenging to identify their cell source in vivo; and 2) recent lineage tracing studies by our lab [14][15][16] and others [17][18][19][20] have shown that marker genes used to identify cell type within lesions are nonspecific. For example, SMC marker genes (e.g. ACTA2) can be expressed by myeloid-derived cells and endothelial cells and SMC can express marker genes of macrophages (e.g. CD68 and LGALS3) [14][15][16][17][18][19][20] . Therefore major unanswered questions remained in the field as to whether SMC are the primary source of collagens in vivo and if SMC produced collagens in turn impact plaque development.We are interested in type XV collagen alpha 1 (COL15A1) as we identified Combined, these results provide the first direct evidence that a SMC-derived collagen, COL15A1, is critical in lesion development. IV DedicationI dedicate this to my grandfather, Arthur Labuz. You were the heart of my family and a testament to hard work, perseverance, and inner strength. I hope I have inherited an ounce of these qualities from you and have made you proud.V Acknowledgements

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The arterial microenvironment: the where and why of atherosclerosis

Cited by 146 publications

References 186 publications

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

L-Carnitine Supplementation Increases Trimethylamine-N-Oxide but not Markers of Atherosclerosis in Healthy Aged Women

Endothelial Glycocalyx: Novel Insight into Atherosclerosis

"Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions"

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