RGD Reference Report - Telmisartan attenuates aortic hypertrophy in hypertensive rats by the modulation of ACE2 and profilin-1 expression. - Rat Genome Database

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Telmisartan attenuates aortic hypertrophy in hypertensive rats by the modulation of ACE2 and profilin-1 expression.

Authors: Zhong, JC  Ye, JY  Jin, HY  Yu, X  Yu, HM  Zhu, DL  Gao, PJ  Huang, DY  Shuster, M  Loibner, H  Guo, JM  Yu, XY  Xiao, BX  Gong, ZH  Penninger, JM  Oudit, GY 
Citation: Zhong JC, etal., Regul Pept. 2011 Jan 17;166(1-3):90-7. doi: 10.1016/j.regpep.2010.09.005. Epub 2010 Sep 18.
RGD ID: 9685442
Pubmed: PMID:20854846   (View Abstract at PubMed)
DOI: DOI:10.1016/j.regpep.2010.09.005   (Journal Full-text)

Profilin-1 has recently been linked to vascular hypertrophy and remodeling. Here, we assessed the hypothesis that angiotensin (Ang) II type I receptor antagonist telmisartan improves vascular hypertrophy by modulation of expression of profilin-1 and angiotensin-converting enzyme 2 (ACE2). Ten-week-old male spontaneously hypertensive rats (SHR) were received oral administration of telmisartan (5 or 10mg/kg; daily) or saline for 10 weeks. Compared with Wistar-Kyoto (WKY) rats, there were marked increases in systolic blood pressure and profilin-1 expression and reduced ACE2 and peroxisome proliferator activated receptor-gamma (PPARgamma) levels in aorta of SHR, associated with elevated extracellular-signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) phosphorylation signaling and aortic hypertrophy characterized with increased media thickness, which were strikingly reversed by telmisartan. In cultured human umbilical artery smooth muscle cells (HUASMCs), Ang II induced a dose-dependent increase in profilin-1 expression, along with decreased ACE2 protein expression and elevated ERK1/2 and JNK phosphorylation. In addition, blockade of ERK1/2 or JNK by either specific inhibitor was able to abolish Ang II-induced ACE2 downregulation and profilin-1 upregulation in HUASMCs. Importantly, treatment with telmisartan (1 or 10 muM) or recombinant human ACE2 (2mg/ml) largely ameliorated Ang II-induced profilin-1 expression and ERK1/2 and JNK phosphorylation and augmented PPARgamma expression in the cultured HUASMCs. In conclusion, telmisartan treatment attenuates vascular hypertrophy in SHR by the modulation of ACE2 and profilin-1 expression with a marked reversal of ERK1/2 and JNK phosphorylation signaling pathways.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOAce2 (Rattus norvegicus)9685442; 9685442mRNA and protein:decreased expression:aortaRGD 
hypertension  IEP 9685442mRNA and protein:decreased expression:aortaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ace2  (angiotensin converting enzyme 2)

Genes (Mus musculus)
Ace2  (angiotensin converting enzyme 2)

Genes (Homo sapiens)
ACE2  (angiotensin converting enzyme 2)


Additional Information