PMID- 11602818
OWN - NLM
STAT- MEDLINE
DCOM- 20011213
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 38
IP  - 5
DP  - 2001 Nov
TI  - Losartan inhibits the angiotensin II-induced modifications on fibrinolysis and 
      matrix deposition by primary human vascular smooth muscle cells.
PG  - 715-28
AB  - Disorders in the fibrinolytic and renin-angiotensin-aldosterone systems and 
      excessive extracellular matrix (ECM) deposition are determinant factors in 
      several pathologic manifestations of vascular and cardiac tissue. We used primary 
      human vascular smooth muscle cells (VSMC) and studied the effects of losartan on 
      angiotensin II (Ang II)-mediated (a) DNA synthesis, (b) secretion of tissue-type 
      plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), (c) 
      secretion of matrix metalloprotease-2 (MMP-2) activity and tissue inhibitors of 
      MMPs (TIMPs), and (d) synthesis of glycosaminoglycans. VSMC cultures, established 
      from human pulmonary arteries, were treated with Ang II (0.1 nM -1 microM ) 
      and/or losartan (0.1-10 microM ), for 24 or 48 h. DNA synthesis was assessed by 
      incorporation of 3 H-thymidine into VSMC, secreted tPA, PAI-1, and TIMPs by 
      enzyme-linked immunosorbent assay, MMP-2 activity by gelatin zymography, and 
      glycosaminoglycan synthesis by 3 H-glucosamine incorporation. Ang II (1 microM ) 
      enhanced DNA synthesis and secretion of PAI-1 and glycosaminoglycans and 
      decreased secretion of MMP-2 activity and tPA, whereas it had no effect on 
      secretion of TIMPs and glycosaminoglycans associated with cell layers. The Ang 
      II-mediated effects were reversed by losartan, in a concentration-dependent 
      manner. Losartan alone increased secretion of tPA, MMP-2 activity, and TIMPs and 
      decreased secretion of PAI-1. These results indicate that AT 1 receptors are 
      implicated in Ang II-mediated disorders of fibrinolysis and excessive ECM 
      deposition by VSMC.
FAU - Papakonstantinou, E
AU  - Papakonstantinou E
AD  - Department of Pharmacology, Aristotle University, Thessaloniki, Greece.
FAU - Roth, M
AU  - Roth M
FAU - Kokkas, B
AU  - Kokkas B
FAU - Papadopoulos, C
AU  - Papadopoulos C
FAU - Karakiulakis, G
AU  - Karakiulakis G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 10028-17-8 (Tritium)
RN  - 11128-99-7 (Angiotensin II)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - JMS50MPO89 (Losartan)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Angiotensin II/antagonists & inhibitors/*pharmacology
MH  - *Angiotensin Receptor Antagonists
MH  - Cells, Cultured
MH  - DNA/biosynthesis
MH  - Extracellular Matrix/*drug effects
MH  - Fibrinolysis/drug effects
MH  - Glycosaminoglycans/metabolism
MH  - Humans
MH  - Losartan/*pharmacology
MH  - Matrix Metalloproteinase 2/analysis/metabolism
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism
MH  - Plasminogen Activator Inhibitor 1/analysis/metabolism
MH  - Pulmonary Artery
MH  - Receptor, Angiotensin, Type 1
MH  - Thymidine/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/analysis/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/analysis/metabolism
MH  - Tissue Plasminogen Activator/analysis/metabolism
MH  - Tritium
EDAT- 2001/10/17 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/17 10:00
PHST- 2001/10/17 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/17 10:00 [entrez]
AID - 10.1097/00005344-200111000-00008 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2001 Nov;38(5):715-28. doi: 
      10.1097/00005344-200111000-00008.