Altered tropomyosin expression in essential hypertension.
Abnormal erythrocyte sodium-lithium countertransport is common in a subgroup of patients with essential hypertension and a strong family history of hypertension and cardiovascular disease. We have previously shown that the abnormality in sodium-lithium countertransport is associated with tropomyosin, a cytoskeletal protein required to stabilize actin filament formation. Leukocyte trafficking events, which depend on cytoskeletal reorganization, are also altered in patients with essential hypertension with abnormal sodium-lithium countertransport. The aim of this study was to determine whether there is an abnormality in isoforms of tropomyosin that are common to erythrocytes and leukocytes. Analysis of reticulocyte RNA by reverse transcription (RT) and polymerase chain reaction (PCR) showed expression of TPMN and TPM5b isoforms of tropomyosin. No other isoforms were expressed. These isoforms were also detected in RNA from leukocytes. In patients with essential hypertension with abnormal erythrocyte sodium-lithium countertransport compared with normal control subjects, there was a higher TPMN/TPM5b ratio of protein in erythrocytes (median 3.8 [range 1.8 to 6.6] versus 2.9 [1.9 to 4.0], P<0.001) and of RNA in leukocytes (3.7 [1.7 to 8.2] versus 2.6 [1.2 to 4.3], P<0.01). Furthermore, the protein ratio of TPMN/TPM5b in erythrocytes showed significant correlation with the V(max)/K(m) ratio of sodium-lithium countertransport across the patient groups (r=-0.42; P<0.01). Therefore, altered tropomyosin expression may be the underlying abnormality associated with blood cell membrane changes in essential hypertension and implicates the cytoskeleton in the pathogenesis of the disease in a major subgroup of patients.
Dunn
Stuart A
SA
Department of Medicine, Medical School, University of Newcastle-Upon-Tyne, Newcastle, England. s.a.dunn@ncl.ac.uk
Mohteshamzadeh
Mobin
M
Daly
Ann K
AK
Thomas
Trevor H
TH
D000368:Aged; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014335:Tropomyosin / Q000235:genetics* / Q000378:metabolism
D017920:Antiporters; D020033:Protein Isoforms; D012333:RNA, Messenger; D014335:Tropomyosin; C045885:sodium-lithium countertransporter