Heart and Vessels

, Volume 15, Issue 3, pp 135–143

Hyperhomocyst(e)inemia induces multiorgan damage

  • Amanda Miller
  • Vibhas Mujumdar
  • Eugene Shek
  • Jason Guillot
  • Mike Angelo
  • Lena Palmer
  • S. C. Tyagi
ORIGINAL ARTICLE

DOI: 10.1007/s003800070030

Cite this article as:
Miller, A., Mujumdar, V., Shek, E. et al. Heart Vessels (2000) 15: 135. doi:10.1007/s003800070030

Abstract

Hyperhomocyst(e)inemia has been associated with the development of hypertension, stroke, and cardiovascular, cerebral/neuronal, renal, and liver diseases. To test the hypothesis that homocyst(e)ine plays an integrated role in multiorgan injury in hypertension, we employed: (1) spontaneously hypertensive rats (SHR) in which endogenous homocyst(e)ine levels are moderately high (18.1 ± 0.5 μM); (2) control age- and sex-matched Wistar Kyoto (WKY) rats in which homocyst(e)ine levels are normal (3.7 ± 0.3 μM). To create the pathophysiological condition of hyperhomocyst(e)inemia, 20 mg/day homocyst(e)ine was administered for 12 weeks in (3) SHR (SHR-H) and in (4) WKY (WKY-H) rats. (5) Endogenous homocyst(e)ine levels were reduced slightly but not significantly from 18.1 ± 0.5 μM to 12.5 ± 0.7 μM in SHR by folic acid administration (SHR-F). Plasma and tissue levels of homocyst(e)ine were determined by HPLC and spectrophotometric methods. Plasma and sympathetic ganglion (neuronal) matrix metalloproteinase (MMP) activity was measured by zymography. Activity of neuronal MMP was increased in hyperhomocyst(e)inemic rats as compared with controls. Mean arterial pressure (mmHg) was 95 ± 5, 126 ± 8, 157 ± 10, 188 ± 5, and 165 ± 12 in WKY, WKY-H, SHR, SHR-H, and SHR-F, respectively. Urinary protein (mg/day) was 0.11 ± 0.03, 0.88 ± 0.22, 0.47 ± 0.10, 0.89 ± 0.21, and 0.81 ± 0.21 in WKY, WKY-H, SHR, SHR-H, and SHR-F, respectively, as measured by the Bio-Rad dye binding assay. The relationships between increased arterial pressure, plasma homocyst(e)ine, and urinary protein were delineated. Plasma and neuronal creatinine phosphokinase (CK) isoenzymes were measured by agarose gel electrophoresis. All three CK isoenzymes, i.e., MM, MB, and BB, specific for skeletal, cardiac, and nerve tissue, respectively, were induced following 12 weeks' hyperhomocyst(e)inemia, suggesting multiorgan injury by homocyst(e)ine. Homocyst(e)ine induces endocardial endothelial cell (capillary) apoptosis and may reduce capillary cell density. Structural damage to aorta, myocardium, kidney, and renal-ureter was analyzed by histology. Results suggested an integrated physiological role of homocyst(e)ine in injury to the endothelial/epithelial cell lining in the respective organs.

Key words Nerve Capillary endothelium Renal-ureter Hypertrophy Heart failure 

Copyright information

© Springer-Verlag Tokyo 2000

Authors and Affiliations

  • Amanda Miller
    • 1
  • Vibhas Mujumdar
    • 1
  • Eugene Shek
    • 1
  • Jason Guillot
    • 1
  • Mike Angelo
    • 1
  • Lena Palmer
    • 1
  • S. C. Tyagi
    • 1
  1. 1.Department of Physiology and Biophysics, School of MedicineThe University of Mississippi Medical CenterMSUSA

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