RGD Reference Report - Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure. - Rat Genome Database

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Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.

Authors: Mujumdar, VS  Tyagi, SC 
Citation: Mujumdar VS and Tyagi SC, J Hypertens. 1999 Feb;17(2):261-70.
RGD ID: 2290471
Pubmed: PMID:10067796   (View Abstract at PubMed)

OBJECTIVE: Extracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio. MATERIALS AND METHODS: We prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure. RESULTS: The elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/- 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P < 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts. CONCLUSIONS: Since collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOTimp4 (Rattus norvegicus)2290471; 2290471 RGD 
Cardiomegaly  IEP 2290471 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Timp4  (TIMP metallopeptidase inhibitor 4)

Genes (Mus musculus)
Timp4  (tissue inhibitor of metalloproteinase 4)

Genes (Homo sapiens)
TIMP4  (TIMP metallopeptidase inhibitor 4)


Additional Information