title: Estrogen effects on MMP-13 and MMP-14 regulation of left ventricular mass in Dahl salt-induced hypertension.
abstract: BACKGROUND
  Female Dahl salt-sensitive (DS) rats fed a low-salt diet develop hypertension at 6 months of age. Ovariectomy at 2 months of age accelerates the development of hypertension, and estrogen replacement delays it. Although acute pressure overload induces structural changes in the left ventricle (LV) further effects of gradual hypertension on LV remodeling have not been examined in the DS rat model.
  
  
  OBJECTIVE
  The purpose of this study was to test the hypothesis that aging and estrogen loss in hypertensive DS rats are accompanied by changes in LV remodeling.
  
  
  METHODS
  Four groups of DS rats were examined: young intact, middle-aged (MA) intact, MA ovariectomized (MA-OVX), and MA-OVX with 17beta-eestradiol (E(2)) supplementation (MA-OVX+E(2)). Myocardial matrix metalloproteinases (MMPs),tissue inhibitors of metalloproteinases (TIMPs),and extracellular matrix (ECM) proteins were assessed by immunoblotting.
  
  
  RESULTS
  Each of the 4 groups comprised 6 animals. Mean (SEM) LV mass was significantly greater in the MA-intact and the MA-OVX groups (1257 [31] mg and 1199 [25] mg, respectively; both, P < 0.05) compared with the young-intact group (697 [6] mg). LV mass in the MA-OVX+E(2) group was significantly lower compared with the MA-intact and MA-OVX groups (both, P < 0.05), suggesting that estrogen may attenuate LV remodeling. Fibronectin and collagen III and IV concentrations increased significantly in the MA-intact and MA-OOVX groups (all, P < 0.05),indicating increased fibrosis. Multiple MMPs also increased in the MA-intact an nd MA-OVX rats, including MMP-3, -7, -99, -113, and -114, and all TIMPs. In contrast, estrogen attenuated fibrosis by increasing MMP-8 concentrations and increasing collagen III fragments. From good-fit regression modeling, MMP-13 and MMP-14 concentrations correlated positively with LV mass for the MA-intact and MA-OVX groups, respectively.
  
  
  CONCLUSIONS
  Gradual hypertension stimulated ECM turnover by increasing both MMP/TIMP production and ECM degradation. Estrogen loss or gain resulted in a shift in MMP profiles, suggesting that MMP-13 and MMP-14 may be differentially regulated in postmenopausal hypertension.
authors.affiliation: Department of Medicine/Cardiology, University of Texas Health Science Center, San Antonio,TX 78229-3900, USA.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Dai
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Teresa
authors.initials: T
authors.lastname: Craig
authors.forename: Youn-Min
authors.initials: YM
authors.lastname: Chou
authors.forename: Carmen
authors.initials: C
authors.lastname: Hinojosa-Laborde
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004039:Diet, Sodium-Restricted; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D010052:Ovariectomy; D017698:Postmenopause; D051381:Rats; D020303:Rats, Inbred Dahl; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D004967:Estrogens; D019714:Tissue Inhibitor of Metalloproteinases; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14