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Altered tropomyosin expression in essential hypertension

Stuart A Dunn1, Mobin Mohteshamzadeh, Ann K Daly

  • 1Department of Medicine, Medical School, University of Newcastle-Upon-Tyne, Newcastle, England. s.a.dunn@ncl.ac.uk

Hypertension (Dallas, Tex. : 1979)
|February 8, 2003
PubMed

Insights

Abnormal erythrocyte sodium-lithium countertransport in essential hypertension is linked to altered tropomyosin expression. This suggests a role for the cytoskeleton in the disease

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Cell Biology

Background:

  • Abnormal erythrocyte sodium-lithium countertransport is prevalent in essential hypertension patients with a family history.
  • This countertransport abnormality is linked to tropomyosin, a cytoskeletal protein crucial for actin filament stability.
  • Leukocyte trafficking, dependent on cytoskeletal reorganization, is also altered in these patients.

Purpose of the Study:

  • To investigate abnormalities in tropomyosin isoforms common to erythrocytes and leukocytes in essential hypertension.
  • To determine if altered tropomyosin expression correlates with sodium-lithium countertransport dysfunction.

Main Methods:

  • Retucylyte RNA was analyzed using reverse transcription (RT) and polymerase chain reaction (PCR) to identify tropomyosin isoforms.
  • Protein and RNA expression levels of TPMN and TPM5b isoforms were quantified in erythrocytes and leukocytes.
  • Statistical analysis, including correlation, was performed to assess relationships between tropomyosin ratios and sodium-lithium countertransport parameters.

Main Results:

  • TPMN and TPM5b were the only expressed tropomyosin isoforms in reticulocytes and leukocytes.
  • Patients with essential hypertension and abnormal sodium-lithium countertransport exhibited a higher TPMN/TPM5b protein ratio in erythrocytes and RNA ratio in leukocytes compared to controls.
  • A significant negative correlation was found between the erythrocyte TPMN/TPM5b protein ratio and the sodium-lithium countertransport V(max)/K(m) ratio.

Conclusions:

  • Altered tropomyosin isoform expression (TPMN/TPM5b ratio) is associated with abnormal erythrocyte sodium-lithium countertransport in essential hypertension.
  • These findings implicate cytoskeletal alterations, specifically tropomyosin, in the pathogenesis of essential hypertension in a significant patient subgroup.
  • This study highlights the role of the cytoskeleton in blood cell membrane abnormalities contributing to essential hypertension.

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