Reversible and irreversible interactions between elastin and plasma lipoproteins

Winlove, C. P.; Parker, Kim H.; Ewins, A. R.

doi:10.1016/0304-4165(85)90237-5

Cited by 15 publications

(3 citation statements)

References 17 publications

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“…17 Others have also documented significant interactions of albumin, lipoproteins, and calcium salts with elastin. 29,30 Such differential binding has several important consequences. First, differential uptake into individual arterial layers causes elastin-rich regions deep in the artery to act as drug sinks and sources, evolving from one to the other in time.…”

Section: Arterial Wall Components Influence Drug Depositionmentioning

confidence: 99%

Arterial Ultrastructure Influences Transport of Locally Delivered Drugs

Hwang

Edelman

2002

Circulation Research

108

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Abstract-An incomplete understanding of the transport forces and local tissue structures that modulate drug distribution has hampered local pharmacotherapies in many organ systems. These issues are especially relevant to arteries, where stent-based delivery allows fine control of locally directed drug release. Local delivery produces tremendous drug concentration gradients and although these are in part derived from transport forces, differences in deposition from tissue to tissue imply that tissue ultrastructure also plays an important role. We measured the equilibrium drug uptake and the penetration and diffusivity of dextrans (a model hydrophilic drug similar to heparin) and albumin in orthogonal planes in arteries explanted from different vascular beds. We found significant variations in drug distribution with geometric orientation and arterial connective tissue content. Drug diffusivities parallel to the connective tissue sheaths were one to two orders of magnitude greater than across these sheaths. This diffusivity difference remained relatively constant for drugs up to 70 kDa before decreasing for larger drugs. Drugs also distributed better into elastic arteries, especially at lower molecular weights, with almost 66% greater transfer into the thoracic aorta than into the carotid artery. Arterial drug transport is thus highly anisotropic and dependent on arterial tissue content.

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Section: Arterial Wall Components Influence Drug Depositionmentioning

confidence: 99%

Arterial Ultrastructure Influences Transport of Locally Delivered Drugs

Hwang

Edelman

2002

Circulation Research

108

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“…The remaining mLDL in the media was possibly distributed into two compartments, one consisting of mLDL irreversibly bound to extracellular matrix components 3940 and the other consisting of mLDL nonspecifically bound to cells. The ability of nLDL to bind nonspecifically to extracellular matrix components 39 and to cells 21 was likely to be the same as that of mLDL. Yet, it is possible that a larger number of nonspecific cellular sites were occupied by mLDLs than by nLDLs, yielding the larger C m than C n observed after the washout period.…”

Section: -mentioning

confidence: 98%

Role of LDL receptors in the in vitro uptake and degradation of LDL in the media of rabbit thoracic aorta.

Curmi

Renaud

et al. 1989

Circulation Research

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The possible role of plasma low-density protein (LDL) receptors in the uptake and degradation of LDL in the whole arterial wall was investigated by comparison of the in vitro uptake of 125I-native LDL (nLDL) and 131I-methylated LDL (mLDL) by the media of deendothelialized rabbit thoracic aorta excised at in vivo length and pressurized to 70 mm Hg, taking the advantage that mLDL is not recognized by the LDL receptor. The distribution of the relative concentrations of nLDL (Cn) and mLDL (Cm) across the wall was obtained using a serial frozen sectioning technique. The aorta was incubated under three different conditions for varying periods of incubation in order to analyze separately the processes of binding, binding-internalization, and degradation. At 39 degrees C, in which binding-internalization and degradation occurred, Cn was significantly higher than Cm at each position across the media. The mean medial Cn/Cm ratio was 1.36 +/- 0.15 (n = 5) after 1 hour of incubation, and decreased to 1.23 +/- 0.22 (n = 7) after 2 hours of incubation and to 1.13 +/- 0.11 (n = 5) after 4 hours of incubation. At 4 degrees C, in which internalization and degradation were blocked, the Cn/Cm ratio reflected the surface nLDL binding alone; the Cn/Cm ratio was 1.47 +/- 0.20 (n = 5) after 4 hours of incubation, higher than the value obtained at 39 degrees C. To investigate whether degradation of nLDL occurred after receptor binding, the interstitial LDL was washed out by an LDL-free solution after 2-hour incubation at 39 degrees C. After 30 minutes of washout, the Cn/Cm ratio decreased to 1.06 +/- 0.20 (n = 5) in the inner media and was unchanged in the outer media. After 1 hour of washout, the ratio declined to 0.57 +/- 0.18 (n = 7) in the inner part of the media and increased progressively to 1 at the media-adventitia boundary. The Cn/Cm ratio, at 0.67 +/- 0.12 (n = 5), was practically constant throughout the media after 2 hours of washout. The nLDL degradation rate across the media was obtained from the comparison of nLDL and mLDL before and after the washout. A steep decreasing gradient in nLDL degradation rate was observed from the luminal to the external surface. The mean medial nLDL degradation rate value was 9.6 +/- 4.5 microliters/cm3 wet tissue/hr. We concluded that functional LDL receptors participate in the uptake and degradation of LDL in the whole aorta.

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“…Lipid deposition adjacent to, and within, elastin fibers has been documented (110,111). Several groups have reported that elastin is capable of interactions with lipoproteins (112,113). Podet et al reported high affinity interactions between human LDL and human aortic elastin with a binding constant of 3.6 x 10 -8 M (114).…”

Section: Elastinmentioning

confidence: 99%

Lipoprotein-matrix interactions in macrovascular disease in diabetes

Tannock

Chait

2004

Front Biosci

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The retention of atherogenic lipoproteins in the artery wall through their interactions with the arterial extracellular matrix is a critical step in the development of atherosclerosis, as outlined in the 'response to retention' hypothesis. Lipoprotein retention by vascular proteoglycans is thought to be the principle means of lipoprotein retention, although lipoprotein binding to other components of the extracellular matrix has been reported. The interactions of lipoproteins and proteoglycans can be direct through ionic interactions between the negatively charged glycosaminoglycan chains of proteoglycans and positively charged residues of apolipoproteins B and E, or can be mediated through bridging molecules such as lipoprotein lipase. Retention of atherogenic lipoproteins within the artery wall environment leads to pathophysiologically important modifications of the lipoproteins, including oxidation. Oxidation of lipoproteins leads to increased uptake by macrophages, leading to the formation of foam cells. This article reviews the scientific evidence in support of the response to retention hypothesis, with a specific focus on the effects of diabetes to modify lipoprotein retention.

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Reversible and irreversible interactions between elastin and plasma lipoproteins

Cited by 15 publications

References 17 publications

Arterial Ultrastructure Influences Transport of Locally Delivered Drugs

Arterial Ultrastructure Influences Transport of Locally Delivered Drugs

Role of LDL receptors in the in vitro uptake and degradation of LDL in the media of rabbit thoracic aorta.

Lipoprotein-matrix interactions in macrovascular disease in diabetes

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