Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis

Authors

  • S Satheesan,

    Corresponding author
    1. Division of Comparative Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
    • Correspondence

      Dr Sangeetha Satheesan, Division of Comparative Medicine/Molecular and Cellular Biology, City of Hope National Medical Center, 1500E Duarte Road, Duarte, CA 91010, USA. E-mail: ssatheesan@coh.org

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  • J L Figarola,

    1. Department of Diabetes, Endocrinology and Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
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  • T Dabbs,

    1. Division of Comparative Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
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  • S Rahbar,

    1. Department of Diabetes, Endocrinology and Metabolism, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
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  • R Ermel

    1. Division of Comparative Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
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Abstract

Background and Purpose

We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology.

Experimental Approach

STZ-induced diabetic rats were treated with or without LR-90 (50 mg L-1 in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra.

Key Results

LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats.

Conclusions and Implications

Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications.

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