RGD Reference Report - [Klotho gene attenuates the progression of hypertension and heart damage in spontaneous hypertensive rats]. - Rat Genome Database

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[Klotho gene attenuates the progression of hypertension and heart damage in spontaneous hypertensive rats].

Authors: Li, Bao-shan  Ma, Hou-xun  Wang, Yan-jiao  Wu, Ping 
Citation: Li BS, etal., Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Dec;29(6):662-8. doi: 10.3760/cma.j.issn.1003-9406.2012.06.008.
RGD ID: 10403062
Pubmed: PMID:23225045   (View Abstract at PubMed)
DOI: DOI:10.3760/cma.j.issn.1003-9406.2012.06.008   (Journal Full-text)


OBJECTIVE: To assess the effect of Klotho gene transduction on the progression of hypertension and heart damage in spontaneous hypertensive rats (SHRs).
METHODS: An adeno-associated virus (AAV) carrying full-length mouse Klotho cDNA (rAAV.mKL) was constructed for in vivo expression of Klotho. Three different groups of male SHRs and a control group of sex and age-matched Sprague Dawley (SD) rats (5 rats per group) were used. The experimental groups of SHRs received an IV injection of phosphate buffered saline (PBS), rAAV.mKL and rAAV.EGFP, respectively. The control group only received equal-volume of PBS. The whole study has spanned 12 weeks. Plasma levels of insulin-like growth factor-1 (IGF-1) and insulin were measured with ELISA. The weight of whole heart was measured to calculate the heart weight index (HWI). EGFP expression of heart frozen sections was observed by fluorescence microscopy. Expression of mRNA and protein of Klotho, IGF-1, IGF-1 receptor (IGF-1R) and p-Akt were determined with RT-PCR, immunohistochemical analysis, and Western blotting. Hypertrophic myocardial cell and collagen fiber were observed by histological examination following Haematoxylin-Eosin and Masson staining.
RESULTS: Transduction of rAAV.mKL can significantly prevent the increase of blood pressure in SHRs. Compared with the control group, the levels of Klotho mRNA and protein have both increased, and the plasma levels of IGF-1, insulin and glucose were elevated, whereas the expression of phosphor-Akt (also called Protein Kinase B, PKB) was decreased in the rAAV.mKL group. Furthermore, a decrease of hypertrophic myocardial cells and collagen fibers was noticed in the rAAV.mKL group compared with the control group.
CONCLUSION: The Klotho gene can attenuate the progression of hypertension and abolishes myocardial hypertrophy and myocardial fibrosis. The protective effect observed in the rAAV.mKL group of SHRs may be attributed to increased Klotho protein and suppression of insulin and IGF-1 signaling pathways through inhibition of Akt phosphorylation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KLHumanCardiomegaly treatmentISOKl (Mus musculus) RGD 
KlRatCardiomegaly treatmentISOKl (Mus musculus) RGD 
KlMouseCardiomegaly treatmentIMP  RGD 
KLHumanhypertension treatmentISOKl (Mus musculus) RGD 
KlRathypertension treatmentISOKl (Mus musculus) RGD 
KlMousehypertension treatmentIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kl  (Klotho)

Genes (Mus musculus)
Kl  (klotho)

Genes (Homo sapiens)
KL  (klotho)


Additional Information