Effects of the angiotensin II receptor blocker losartan on the monocyte expression of biglycan in hypertensive patients.
1. Recently, we demonstrated that biglycan (BGN) is increased in circulating monocyte cells from hypertensive patients and that angiotensin (Ang) II is able to increase BGN expression. The present study was designed to investigate the effects of treatment with the angiotensin AT(1) receptor antagonist losartan on monocyte BGN mRNA and protein expression in essential hypertension. 2. One hundred and twenty-six newly diagnosed hypertensive patients without additional risk factors for atherosclerosis and cardiovascular disease were treated with 100 mg losartan once daily for 6 months. Biglycan mRNA and protein expression was determined in monocytes isolated from peripheral blood before (T(0)) and after (T(1)) therapy. Plasma levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and high sensitivity C-reactive protein (hs-CRP) were also determined. In addition, BGN mRNA and protein expression was determined after the ex vivo addition of 1 micromol/L AngII to monocytes isolated from 20 randomly selected hypertensive patients. 3. Biglycan mRNA and protein expression, blood pressure and plasma levels of fibrinogen, IL-6, TNF-alpha and CRP were significantly lower at T(1) than at T(0). Variations in BGN expression were associated with inflammatory markers, but not directly with blood pressure. In AngII-stimulated monocytes, BGN mRNA and protein expression was significantly lower at T(1) that at T(0). Moreover, mean BGN mRNA expression in AngII-stimulated monocytes isolated from losartan-treated patients was similar to baseline expression in unstimulated monocytes from untreated patients. 4. The results of the present study show that losartan can reduce BGN expression in monocytes from hypertensive patients, without any linear association with blood pressure, suggesting that the effects of AngII on BGN expression in monocytes may be modulated, in part, by an AT(1) receptor blocker.
Sardo
Maria A
MA
Department of Internal Medicine, University of Messina, Messina, Italy.
Mandraffino
Giuseppe
G
Riggio
Stefania
S
D'Ascola
Angela
A
Alibrandi
Angela
A
Saitta
Carlo
C
Imbalzano
Egidio
E
Castaldo
Maria
M
Cinquegrani
Maurizio
M
Saitta
Antonino
A
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D058578:Biglycan / Q000096:biosynthesis* / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D047228:Angiotensin II Type 1 Receptor Blockers; D058578:Biglycan; D015850:Interleukin-6; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D002097:C-Reactive Protein; D019808:Losartan