The pathogenesis of atherosclerosis: An overview

Schwartz, Colin J.; Valente, Anthony J.; Sprague, Eugene A.; Kelley, Jim; Nerem, Robert M.

doi:10.1002/clc.4960141302

Cited by 265 publications

(150 citation statements)

References 91 publications

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“…Atherosclerosis occurs mainly in locations of disturbed blood flow patterns [9,47]. The local transport of several substances near and at the vessel wall are known to influence atherosclerosis progression [56].…”

Section: Introductionmentioning

confidence: 99%

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

Arzani

Gambaruto

Chen

et al. 2016

Biomech Model Mechanobiol

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms suitable in regions of complex hemodynamics that are traditionally difficult to quantify, yet encountered in many disease scenarios. Keywords: advection-diffusion; blood flow; hemodynamics; near-wall transport; residence time; shear stress; p. 2 IntroductionBiomechanical interactions between blood flow and the vessel wall are central to the initiation and progression of most cardiovascular diseases. Indeed, the majority of computational and experimental investigations into blood flow seek to understand how local flow mechanics relates to disease progression in or on the vessel wall. Blood flow conditions in diseased vessels are usually spatially and temporally complex and are challenging to characterize [51,50], even without reference to the coupled biochemical or biophysical processes driving disease progression. Nonetheless, the role of blood flow mechanics in the "near-wall" region is of utmost importance since this is where such couplings are most profound. In the near-wall region, blood flow serves to impart mechanical stresses on the vessel wall, as well as regulate the local transport of reactive material between the tissue and fluid domains. It is this latter mechanism that motivates the work presented herein.A compelling scenario involving the interaction between blood flow and the vessel wall is atherosclerosis, which is a leading cause of death worldwide. Atherosclerosis occurs mainly in locations of disturbed blood flow patterns [9,47]. The local transport of several substances near and at the vessel wall are known to influence atherosclerosis progression [56]. For example, previous studies have looked into transport of low density lipoproteins (LDL) [17,20,30,14], high density lipoproteins (HDL) [40,24], oxygen [16,27], nitric oxide (NO) [45,35], monocytes [12,14], and adenine triphosphate ATP and adenine diphosphate ADP [13,15,8] as important mass transport processes involved in atherosclerosis.Intravascular thrombosis is another compelling pathology associated with most cardiovascular diseases where near-wall transport becomes important [7,25]. The trajectories of individual platelets and the accumulation and residence time of chemical solutes including ADP, thrombin, and various blood factors control clot formation. These solutes, and especially in activated form, are generated at the vessel wall or from bound platelets. Complex hemodynamics and flow stagnation are often associated with prothrombotic conditions. For example, intraluminal thrombus in abdominal aortic aneurysm (AAA) [57,54] complicates disease progression, and is thought to be strongly coupled to flow stagnation and recirculation. The chaotic flow field in AAAs [3] Near-wall transport can either be (i) explicitly modeled for a specific transport problem, or (ii) inferred from appropriate hemodynamics meas...

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Section: Introductionmentioning

confidence: 99%

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

Arzani

Gambaruto

Chen

et al. 2016

Biomech Model Mechanobiol

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“…Expression of MCP-1 has been associated with a variety of human diseases, such as atherosclerosis, rheumatoid arthritis, HIV replication, and prostate adenocarcinoma (5)(6)(7)(8). MCP-1 expression is induced in numerous cell types by inflammatory mediators, such as TNF (9), platelet-derived growth factor (PDGF) BB (10), IL-1 (11), and IFN-␥ (12).…”

mentioning

confidence: 99%

Communication Between NF-κB and Sp1 Controls Histone Acetylation Within the Proximal Promoter of the Monocyte Chemoattractant Protein 1 Gene

Boekhoudt

Guo

Beresford

et al. 2003

The Journal of Immunology

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The induction of the monocyte chemoattractant protein 1 gene (MCP-1) by TNF occurs through an NF-κB-dependent distal regulatory region and an Sp1-dependent proximal regulatory region that are separated by 2.2 kb of sequence. To investigate how these regions coordinate activation of MCP-1 in response to TNF, experiments were performed to examine the role of coactivators, changes in local chromatin structure, and the acetylation of histones at the MCP-1 regulatory regions. An E1a-sensitive coactivator was found to be required for expression. In vivo nuclease sensitivity assays identified changes in response to TNF at both the proximal and distal regions that were dependent on the p65 subunit of NF-κB and Sp1. Chromatin immunoprecipitations used to analyze factor assembly and histone acetylation at the distal and proximal regions showed that Sp1 binding to and histone acetylation of the proximal region was dependent on NF-κB p65. Conversely, Sp1 assembly at the proximal region was required for p65 binding to and acetylation of the distal region, suggesting communication between the two regions during gene activation. These data and the NF-κB p65-dependent histone acetylation of a middle region sequence suggest a potential order for the assembly, acetylation and accessibility of the MCP-1 regulatory regions in response to TNF.

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“…The importance of a functionally intact endothelium in atherosclerosis is firmly established. 20 Less well characterized, however, is the role of the endothelium in extracellular matrix metabolism, despite the observation that the extracellular matrix comprises the bulk of the media in health and the bulk of the abnormal neointima during disease.…”

mentioning

confidence: 99%

Vascular Endothelial Cell Regulation of Extracellular Matrix Collagen

Myers

Tanner

1998

ATVB

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Abstract-Endothelium-derived products have been implicated in the regulation of vascular wall structure through their effects on extracellular matrix metabolism. The purpose of this study was to further understand the paracrine mechanisms underlying endothelial cell regulation of extracellular matrix metabolism by testing the hypothesis that endothelium-derived nitric oxide decreases the concentration of soluble collagens derived from vascular smooth muscle cells (VSMCs). Porcine coronary endothelium and VSMCs were grown under a coculture configuration to assess the paracrine effects of nitric oxide produced by the endothelium on VSMC collagen types I and III. Endogenous endothelial cell nitric oxide production was blocked with N -nitro-L-arginine methyl ester. Collagen type I and type III were quantitatively measured using an enzyme-linked immunosorbent assay method. The endothelium elicited a timedependent increase in the concentration of soluble VSMC-derived collagen type I; in contrast, collagen type III was decreased. After inhibition of nitric oxide production, there was a marked increase in both collagen types I and III concentration. These results demonstrated that endothelium-derived nitric oxide differentially alters collagen subtypes produced by VSMCs. The data support the hypothesis that nitric oxide functions via a paracrine mechanism to decrease VSMC collagen types I and III concentration, a finding consistent with an integral role for the endothelium in modulating extracellular matrix metabolism. (Arterioscler Thromb Vasc Biol. 1998;18:717-722.) Key Words: extracellular matrix Ⅲ nitric oxide Ⅲ collagen Ⅲ endothelium N itric oxide is an endothelium-derived compound that exerts multiple effects on the vasculature through its paracrine actions on the vessel wall, as well as on formed blood elements. The vasomotor actions of NO are well characterized (for review, see Reference 1). Nitric oxide also is a potent inhibitor of platelet aggregation, 2,3 an antimitogen, 4-7 an inhibitor of cell migration, 8 and an immunomodulator.9 -11 Alterations and/or abnormalities in NO metabolism have been implicated in a variety of diseases, especially atherosclerosis 12-15 and, more recently, restenosis. 16,17 The multiple actions of NO and its role in vascular wall disease are consistent with an important role in the metabolism of the extracellular matrix.The vascular wall extracellular matrix comprises the bulk of the interstitium of the media and is composed of a complex mixture of extracellular matrix proteins, including collagens. 18 The fibrillar collagens are the most abundant collagens, with subtypes I, III, and IV being most common. 18,19 Atherogenesis and restenosis are two disease processes relevant to coronary artery vascular biology that are directly related to extracellular matrix collagen synthesis and degradation, primarily because the hallmark of the disease is mechanical obstruction of coronary blood flow secondary to medial and intimal hyperplasia. The importance of a functionally intact endotheliu...

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The pathogenesis of atherosclerosis: An overview

Cited by 265 publications

References 91 publications

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

Wall shear stress exposure time: a Lagrangian measure of near-wall stagnation and concentration in cardiovascular flows

Communication Between NF-κB and Sp1 Controls Histone Acetylation Within the Proximal Promoter of the Monocyte Chemoattractant Protein 1 Gene

Vascular Endothelial Cell Regulation of Extracellular Matrix Collagen

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