TITLE

Reduction of arteriosclerotic nanoplaque formation and size by fluvastatin in a receptor-based biosensor model

AUTHOR(S)
Siegel, G.; Abletshauser, C.; Malmsten, M.; Schmidt, A.; Winkler, K.
PUB. DATE
June 2003
SOURCE
Cardiovascular Research;Jun2003, Vol. 58 Issue 3, p696
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Proteoheparan sulfate can be adsorbed onto a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques suggesting that HDL has a high binding affinity and a protective effect on interfacial heparan sulfate proteoglycan layers with respect to LDL and Ca2+ complexation. LDL was found to be deposited strongly at the proteoheparan sulfate-coated surface, particularly in the presence of Ca2+, apparently through complex formation ‘proteoglycan–low density lipoprotein–calcium’. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. In a receptor-based biosensor application, this system was tested on its reliability to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The VLDL/IDL/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high risk patient with dyslipoproteinaemia and type 2 diabetes mellitus showed the start of arteriosclerotic nanoplaque formation at a normal blood Ca2+ concentration, with a strong increase at higher Ca2+ concentrations. Nanoplaque formation and size of the HDL-containing lipid fraction remained well below that of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the patient (one single 80 mg slow release matrix tablet) or in a 2-month medication regimen, markedly slowed down this process of ternary aggregational nanoplaque build-up and substantially inhibited nanoplaque size development at all Ca2+ concentrations used. The acute action gave no significant change in lipid concentrations of the patient. Furthermore, after nanoplaque generation, fluvastatin, similar to HDL, was able to reduce nanoplaque formation and size. These immediate effects of fluvastatin have to be taken into consideration when interpreting the clinical outcome of long-term studies.
ACCESSION #
9952601

 

Related Articles

  • Lipoprotein(a) and atherogenesis: a puzzle inside a riddle within an enigma. Sniderman, Allan D. // Clinical & Investigative Medicine;Jun2002, Vol. 25 Issue 3, p89 

    Comments on a study on the role of lipoprotein(a) in coronary atherosclerosis. Conclusion reached by the study; Facts about lipoprotein(a); Lessons that can be learned from the study.

  • The lipoproteins: predictors, protectors, and pathogens. Lewis, Barry // British Medical Journal (Clinical Research Edition);10/22/1983, Vol. 287 Issue 6400, p1161 

    Examines the mechanisms of lipoproteins. Contributions of low density lipoproteins to other aspects of atherosclerosis; Factors determining plasma concentrations of lipoproteins; Effects of increased high density lipoproteins on metabolic events.

  • Severity of coronary atherosclerosis related to lipoprotein concentration. Jenkins, P.J.; Harper, R.W.; Nestel, P.J. // British Medical Journal;8/5/1978, Vol. 2 Issue 6134, p388 

    Examines the influence of lipoprotein concentration on the severity of coronary atherosclerosis. Method used to quantify the extent of atherosclerosis; Importance of lipoproteins in predicting coronary heart disease; Correlation between age and lipoprotein concentration.

  • Do oxidized lipoproteins contribute to glomerulosclerosis? Gröne, Hermann-Josef // Kidney International;Sep1998, Vol. 54 Issue 3, p995 

    Editorial. Examines the association of lipoproteins with atherosclerosis. Effects of lipoproteins with abnormal composition on mesangial cells and podocytes; Localization of malondialdehyde modified proteins; Relationship between tubulointerstitial damage and hyperlipoproteinemia.

  • The Author Replies:. Massy, Ziad A // Kidney International;Mar2014, Vol. 85 Issue 3, p712 

    A response from the author of the article related to low levels and composition of high-density lipoprotein (HDL) in the atherosclerosis in the previous issue is presented.

  • Cholesterol?Atherosclerosis Is Kaput!  // Health & Stress;2002, Issue 8, p4 

    Focuses on the link between low-density cholesterol (LDL) and atherosclerosis. Effect of dietary fat on blood cholesterol; Coronary heart disease; Effects of statins.

  • Lipoprotein(a) and atherosclerosis. Scanu, Angelo M.; Lawn, Richard M.; Berg, Kare; Scanu, A M; Lawn, R M; Berg, K // Annals of Internal Medicine;8/1/91, Vol. 115 Issue 3, p209 

    Lipoprotein(a) [Lp(a)], a lipoprotein variant, was relegated for almost 25 years to the study of a few specialists. During the past 3 to 4 years, however, there has been a tremendous upsurge of interest in Lp(a), primarily because of multidisciplinary efforts in structural and molecular biology....

  • Modulation of ERG25 expression by LDL in vascular cells. Rodriguez, C.; Raposo, B.; Martinez-Gonz�lez, J.; Llorente-Cort�s, V.; Vilahur, G.; Badimon, L. // Cardiovascular Research;Apr2003, Vol. 58 Issue 1, p178 

    Background: Plasma low density lipoproteins (LDL) play a key role in the pathogenesis of atherosclerosis. LDL modify gene expression in vascular cells leading to disturbances in the functional state of the vessel wall. Methods: Expression levels of C-4 sterol methyl oxidase gene...

  • Modulation of endothelial Ca2+-activated K+ channels by oxidized LDL and its contribution to endothelial proliferation Kuhlmann, Christoph Rüdiger Wolfram; Schäfer, Matthias; Li, Fang; Sawamura, Tatsuya; Tillmanns, Harald; Waldecker, Bernd; Wiecha, Johannes // Cardiovascular Research;Dec2003, Vol. 60 Issue 3, p626 

    Objective: Oxidized low-density lipoprotein (oxLDL) plays an important role in causing endothelial dysfunction and initiating atherosclerosis. Some of the endothelial functions have been shown to be modulated by changes in cellular electrophysiological properties. Therefore, we analysed the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics