Document Detail

Consistent Alterations of Circulating Matrix Metalloproteinases Levels in Untreated Hypertensives and in Spontaneously Hypertensive Rats: A Relevant Pharmacological Target.
MedLine Citation:
PMID:  21401887     Owner:  NLM     Status:  Publisher    
  Inconsistent matrix metalloproteinases (MMPs) levels have been reported in hypertension, with higher, similar and lower MMPs levels reported in hypertensives compared with normotensives. Differences between studies may reflect lack of control of drug effects, accompanying diseases and pre-analytical issues. We compared MMP-2, MMP-8 and MMP-9 levels in 38 untreated hypertensive patients (with no other diseases) with those found in 33 normotensive controls. We also studied endogenous MMPs inhibitors (TIMP-1, TIMP-2 and alpha-2-macroglobulin-A2M). Additionally, we assessed MMPs and A2M levels in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. We hypothesized that similar MMPs/endogenous inhibitors profiles would be found in this animal model of hypertension and in clinical hypertension. MMPs, TIMPs and A2M were measured in plasma samples with commercially available ELISA and gelatin zymography. We found unaltered MMP-2, MMP-8, TIMP-1, TIMP-2 and A2M levels in hypertension. However, hypertensives had higher MMP-9 levels and MMP-9/A2M ratios than normotensives. Moreover, while we found similar MMP-2 and A2M levels in SHR and WKY rats, we found higher MMP-9 levels and MMP-9/A2M ratios in SHR versus WKY rats. These findings show consistent abnormal net plasma MMP-9 (but not MMP-2) activity in clinical and experimental hypertension. These parallel alterations in clinical hypertension and in SHR suggest an important role for MMPs in hypertension. While MMPs may be a relevant pharmacological target, antihypertensive drugs that down-regulate MMPs may offer advantages in the management of this disease.
Vanessa Fontana; Pamela S Silva; Vanessa A Belo; Raquel C Antonio; Carla S Ceron; Celso Biagi; Raquel F Gerlach; Jose E Tanus-Santos
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-15
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  -     ISSN:  1742-7843     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil Department of Pharmacology, Faculty of Medicinal Sciences, University of Campinas, State University of Campinas, Campinas, SP, Brazil Santa Casa of Araçatuba, Araçatuba, SP, Brazil Department of Morphology, Estomatology and Physiology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
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