A novel pleiotropic effect of atorvastatin on advanced glycation end product (AGE)-related disorders

S. Yamagishi, K. Nakamura, T. Matsui, Hiroyoshi Inoue

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Reducing sugars can react non-enzymatically with the amino groups of proteins to form reversible Schiff bases, and then Amadori products. These early glycation products undergo further complex reactions such as rearrangement, dehydration and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives termed "advanced glycation end products" (AGEs). The pathological role of the non-enzymatic glycation of proteins has become increasingly evident in various types of disorders such as diabetic vascular complications, neurodegenerative diseases, and melanoma growth and metastasis. Furthermore, there is a growing body of evidence that RAGE is a signal-transducing receptor for AGEs and that engagement of RAGE with AGEs evokes oxidative stress and vascular inflammation, thereby being involved in the AGE-related disorders. We have recently found that atorvastatin, a lipid-lowering agent decreases serum levels of AGEs in type 2 diabetic patients in a cholesterol-lowering independent manner. Further, we have shown that atorvastain blocks the AGE-signaling to C-reactive protein (CRP) expression in human hepatoma cells in vitro via anti-oxidative properties. These observations led us to speculate that atorvastatin could be a promising remedy for treating patients with AGE-related disorders. In this paper, we would like to propose the possible ways of testing our hypotheses. (1) Does atorvastatin treatment reduce the development and progression of diabetic vascular complications with normocholesterolemic patients? If the answer is yes, is this beneficial effect of atorvastatin superior to that of other cholesterol-lowering agents with equihypolipidemic properties? (2) Are these beneficial effects of atorvastain attributed to its AGE-lowing properties? Does the blockade by atorvastain of the AGE signaling pathway, in other words, the suppression of 8-hydroxydeoxyguanosine and CRP levels by atorvastatin treatment, contribute to its cardioprotective properties? (3) Does the treatment with atorvastatin decrease the incidence of neurodegenerative disorders such as Alzheimer's disease and/or prolong the survival of these patients? (4) How about the effects of atorvastatin on the incidence of malignant melanoma? These prospective studies will provide further valuable information whether the blockade by atorvastatin of the AGE formation or the AGE-downstream signaling could be clinically relevant.

Original languageEnglish
Pages (from-to)338-340
Number of pages3
JournalMedical Hypotheses
Volume69
Issue number2
DOIs
Publication statusPublished - 2007
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Diabetic Angiopathies
Neurodegenerative Diseases
C-Reactive Protein
Melanoma
Cholesterol
Schiff Bases
Atorvastatin Calcium
Incidence
Dehydration
Blood Vessels
Hepatocellular Carcinoma
Alzheimer Disease
Proteins
Oxidative Stress
Therapeutics
Prospective Studies
Neoplasm Metastasis
Inflammation
Lipids

ASJC Scopus subject areas

  • Developmental Biology
  • Medicine(all)
  • Drug Discovery

Cite this

A novel pleiotropic effect of atorvastatin on advanced glycation end product (AGE)-related disorders. / Yamagishi, S.; Nakamura, K.; Matsui, T.; Inoue, Hiroyoshi.

In: Medical Hypotheses, Vol. 69, No. 2, 2007, p. 338-340.

Research output: Contribution to journalArticle

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