Effects of early and late chronic pressure overload on extracellular matrix remodeling.
The left ventricle (LV) remodels with age and in response to pressure overload. While aging and pressure overload are superimposed in the clinical context, the structural and functional consequences of the individual processes are not well-understood. Accordingly, the objective of this study was to compare the effects of both early and late chronic hypertension on extracellular matrix (ECM) remodeling. The following groups of Dahl rats were studied: 1) young salt-resistant (control, n=6); 2) young salt-sensitive (early phase of chronic hypertension, n=6); 3) middle-aged salt-resistant (aging, n=5); and 4) middle-aged salt-sensitive (late phase of chronic hypertension, n=6). We measured LV mass (LVM) and body weight (BW) and immunoblotted a panel of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and ECM proteins. Total collagen increased, several MMPs decreased, and TIMP-1 increased in the early phase of hypertension, consistent with fibrosis. Active MMP-8 decreased from 8,010+/-81 U in young salt-resistant to 5,260+/-313 U in young salt-sensitive (p<0.05) rats. During the late phase, chronic hypertension decreased total collagen levels and increased MMP-8 and MMP-14 (all p<0.05). Based on good-fit modeling analysis, MMP-14 (45 kDa) correlated positively with changes in LVM/BW during the early phase. In conclusion, this is the first study to evaluate MMP levels during both early and late chronic phases of hypertension. Our results highlight that ECM remodeling in response to pressure overload is a dynamic process involving excessive ECM accumulation and degradation.
Lin
Jing
J
Department of Medicine, Division of Cardiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Davis
Harrison B
HB
Dai
Qiuxia
Q
Chou
Youn-Min
YM
Craig
Teresa
T
Hinojosa-Laborde
Carmen
C
Lindsey
Merry L
ML
D000818:Animals; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D015151:Immunoblotting; D053508:Matrix Metalloproteinase 12 / Q000032:analysis; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D051381:Rats; D020303:Rats, Inbred Dahl; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis
D019714:Tissue Inhibitor of Metalloproteinases; D053508:Matrix Metalloproteinase 12; D053511:Matrix Metalloproteinase 14