Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue.

ABSTRACT:

Objective

To examine the role of aldo-keto reductases (AKRs) in the cardiovascular metabolism of the precursors of advanced glycation end products (AGEs).

Research design and methods

Steady-state kinetic parameters of AKRs with AGE precursors were determined using recombinant proteins expressed in bacteria. Metabolism of methylglyoxal and AGE accumulation were studied in human umbilical vein endothelial cells (HUVECs) and C57 wild-type, akr1b3 (aldose reductase)-null, cardiospecific-akr1b4 (rat aldose reductase), and akr1b8 (FR-1)-transgenic mice. AGE accumulation and atherosclerotic lesions were studied 12 weeks after streptozotocin treatment of C57, akr1b3-null, and apoE- and akr1b3-apoE-null mice.

Results

Higher levels of AGEs were generated in the cytosol than at

SUBMITTER: Baba SP 

PROVIDER: S-EPMC2768164 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature