RGD Reference Report - Hypertension-mediated albuminuria is associated with reduced lysosomal activity in the kidney and the heart. - Rat Genome Database

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Hypertension-mediated albuminuria is associated with reduced lysosomal activity in the kidney and the heart.

Authors: Hilliard, LM  Russo, LM  Comper, WD 
Citation: Hilliard LM, etal., Am J Nephrol. 2009;29(5):454-64. Epub 2008 Nov 21.
RGD ID: 2315726
Pubmed: PMID:19023196   (View Abstract at PubMed)
DOI: DOI:10.1159/000176535   (Journal Full-text)

BACKGROUND: Recent studies suggest that expression of the transforming growth factor-beta (TGF-beta)-inducible gene-h3 (betaig-h3) and its anti-lysosomal activity may be responsible for the development of albuminuria and cardiovascular disease associated with hypertension. METHODS: We evaluated the proposed linkage using the spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat models. The kidney and left ventricular weight/body weight ratios were measured and cardiac collagen deposition was analyzed by Masson's trichrome stain. Renal and cardiac TGF-beta(1) and betaig-h3 expression were determined by real-time reverse transcription-polymerase chain reaction, and renal and cardiac cathepsin B and L activities were measured as an indicator of lysosomal proteolytic activity. RESULTS: SHR exhibited increased levels of intact urinary albumin without significant change in total albumin (intact plus albumin-derived material) excretion. This was accompanied by renal hypertrophy, increased renal betaig-h3 expression, and reduced renal cathepsin B and L activities. At the same time, increased cardiac TGF-beta(1) and betaig-h3 expression and reduced cardiac cathepsin B activity was identified in SHR in addition to cardiac hypertrophy and increased collagen deposition. All these changes could be ameliorated with ramipril treatment. CONCLUSIONS: These findings implicate for the first time betaig-h3 expression and lysosomal activity as a key factor in the induction of albuminuria and cardiovascular disease associated with hypertension.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CTSBHumanAlbuminuria  ISOCtsb (Rattus norvegicus)associated with HypertensionRGD 
CTSLHumanAlbuminuria  ISOCtsl (Rattus norvegicus)associated with HypertensionRGD 
CtsbRatAlbuminuria  IDA associated with HypertensionRGD 
CtsbMouseAlbuminuria  ISOCtsb (Rattus norvegicus)associated with HypertensionRGD 
CtslRatAlbuminuria  IDA associated with HypertensionRGD 
CtslMouseAlbuminuria  ISOCtsl (Rattus norvegicus)associated with HypertensionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctsb  (cathepsin B)
Ctsl  (cathepsin L)

Genes (Mus musculus)
Ctsb  (cathepsin B)
Ctsl  (cathepsin L)

Genes (Homo sapiens)
CTSB  (cathepsin B)
CTSL  (cathepsin L)


Additional Information