Rate-Limiting Steps in the Development of Atherosclerosis: The Response-to-Influx Theory

Weinberg, Peter D.

doi:10.1159/000076124

Cited by 36 publications

(24 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other investigators have argued that lipoprotein permeation becomes an increasingly important variable as lesions progress and may be a relevant factor in human atherosclerosis. 82,83 The uncertainty in this area allows us to only speculate about therapeutic opportunities. Previous work has suggested that blood pressure lowering, an important clinical intervention, reduced endothelial permeability to LDL.…”

Section: Lipoprotein Properties and Endothelial Permeabilitymentioning

confidence: 99%

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis

2007

View full text Add to dashboard Cite

Abstract-The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Local biological responses to these retained lipoproteins, including a chronic and maladaptive macrophageand T-cell-dominated inflammatory response, promote subsequent lesion development. The most effective therapy against atherothrombotic cardiovascular disease to date-low density lipoprotein-lowering drugs-is based on the principle that decreasing circulating apolipoprotein B lipoproteins decreases the probability that they will enter and be retained in the subendothelium. Ongoing improvements in this area include more aggressive lowering of low-density lipoprotein and other atherogenic lipoproteins in the plasma and initiation of low-density lipoprotein-lowering therapy at an earlier age in at-risk individuals. Potential future therapeutic approaches include attempts to block the interaction of apolipoprotein B lipoproteins with the specific subendothelial matrix molecules that mediate retention and to interfere with accessory molecules within the arterial wall that promote retention such as lipoprotein lipase, secretory sphingomyelinase, and secretory phospholipase A 2 . Although not the primary focus of this review, therapeutic strategies that target the proatherogenic responses to retained lipoproteins and that promote the removal of atherogenic components of retained lipoproteins also hold promise. The finding that certain human populations of individuals who maintain lifelong low plasma levels of apolipoprotein B lipoproteins have an Ϸ90% decreased risk of coronary artery disease gives hope that our further understanding of the pathogenesis of this leading killer could lead to its eradication.

show abstract

Section: Lipoprotein Properties and Endothelial Permeabilitymentioning

confidence: 99%

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis

2007

View full text Add to dashboard Cite

show abstract

“…Staining was then examined in areas around arterial branch points; the strikingly nonuniform distribution of lipid deposition seen in such areas may reveal pathological mechanisms and has attracted considerable interest (reviewed by Weinberg 2004). The thoracic aorta from each animal was opened along its ventral wall so that the origins of four randomly-chosen intercostal arteries could be examined with each technique.…”

Section: Surgical and Lipid-staining Proceduresmentioning

confidence: 99%

Use of a desktop scanner and spreadsheet software for mapping arterial disease

Cremers

Weinberg

2006

Scanning

Self Cite

View full text Add to dashboard Cite

Summary:Mapping the surface area and distribution of atherosclerosis has so far required photographic, video, or photomicrographic imaging of the inner surface of the arterial wall, as well as laborious manual or sophisticated image processing methods of quantification. We investigated whether comparable results could be obtained by using a conventional flatbed scanner and readily available spreadsheet software. Lipid-rich lesions near 21 aortic branches from cholesterol-fed rabbits were mapped using a scanner-based technique and an established photomicrographic technique. When the tissue was counterstained and held on the scanner by a transparent weight to obtain adequate contrast and prevent detection of adventitial staining, the areas of lipid deposition detected by the two methods correlated highly (R 2 =0.99). Discrepancies arose mainly at the edges of lesions, probably because of alignment errors and better flattening of the tissue on the scanner; when these were accounted for, discrepancies occurred in <1% of the total area examined. The new method produces results comparable with previous procedures, but is much more rapid and requires only office equipment and software.

show abstract

“…The disease is characterised by a build up of lipid, inflammatory cells and fibrous proteins in the intima and inner media of the arterial wall. The precise mechanisms involved in the development of the disease, especially in its early stages, are still disputed, but the uptake of lipid-carrying plasma macromolecules is thought to play a key role (Nielsen, 1996, Weinberg, 2004, Tarbell, 2003, 2010; hence, studies of the rate of entry and transport within the wall of macromolecules could increase our understanding of the disease. Water transport, the subject of this paper, is important because much macromolecule transport is convective (A.…”

Section: Introductionmentioning

confidence: 99%

A combined numerical and experimental framework for determining permeability properties of the arterial media

Comerford

Chooi

Nowak

et al. 2014

Biomech Model Mechanobiol

View full text Add to dashboard Cite

The medial layer of the arterial wall may play an important role in the regulation of water and solute transport across the wall. In particular, a high medial resistance to transport could cause accumulation of lipid carrying molecules in the inner wall. In this study, the water transport properties of medial tissue were characterised in a numerical model utilising experimentally obtained data for the medial microstructure and the relative permeability of di↵erent constituents. For the model, a new solver for flow in porous materials, based on a high-order splitting scheme, was implemented in the spectral/hp element library nektar++ and validated. The data were obtained by immersing excised aortic bifurcations in a solution of fluorescent protein tracer and subsequently imaging them with a confocal microscope. Cuboidal regions of interest were selected in which the microstructure and relative permeability of di↵erent structures were transformed to a computational mesh. Impermeable objects were treated fictitiously in the numerical scheme. On this cube, a pressure drop was applied in the three coordinate directions and the principal components of the permeability tensor were determined. The reconstructed images demonstrated the arrangement of elastic lamellae and interspersed smooth muscle cells in rat aortic media; the distribution and alignment of the smooth muscle cells varied spatially within the extracellular matrix. The numerical simulations high-

show abstract

Rate-Limiting Steps in the Development of Atherosclerosis: The Response-to-Influx Theory

Cited by 36 publications

References 51 publications

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis

Use of a desktop scanner and spreadsheet software for mapping arterial disease

A combined numerical and experimental framework for determining permeability properties of the arterial media

Contact Info

Product

Resources

About