RGD Reference Report - Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells. - Rat Genome Database

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Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells.

Authors: Liu, G  Hitomi, H  Hosomi, N  Lei, B  Pelisch, N  Nakano, D  Kiyomoto, H  Ma, H  Nishiyama, A 
Citation: Liu G, etal., Hypertens Res. 2010 Dec;33(12):1250-7. Epub 2010 Oct 7.
RGD ID: 5131524
Pubmed: PMID:20927110   (View Abstract at PubMed)
DOI: DOI:10.1038/hr.2010.187   (Journal Full-text)

Angiotensin II (AngII) stimulates vascular smooth muscle cell (VSMC) proliferation; however, the effect of AngII on cell proliferation in the presence of mechanical force is not clear. We investigated the mechanism of AngII-induced cell proliferation mediated by mechanical stretch in VSMCs of both normotensive and hypertensive rats. VSMCs obtained from the thoracic aortas of 8-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were stretched by a Flex culture system. Mechanical stretch significantly upregulated protein expression of AngII type 1 (AT) receptor, epidermal growth factor (EGF) receptor and mitogen-activated protein kinase phosphatase-1 in both SHR and WKY VSMCs; however, there was no significant difference in these changes between the cells from SHR and WKY. Mechanical stretch attenuated AngII-induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, ERK kinase (MEK) and EGF receptor; it also attenuated [(3)H] thymidine incorporation and cell proliferation in VSMC of WKY. In contrast, the effects of AngII were augmented by mechanical stretch in VSMC of SHR. AngII-induced ERK 1/2 phosphorylation and cell proliferation in SHR were inhibited by pretreatment with an AT receptor blocker, candesartan and an inhibitor of MEK, PD98059. Moreover, pretreatment with an EGF receptor tyrosine kinase inhibitor, AG1478, also blocked upregulation of AngII-induced ERK 1/2 phosphorylation induced by stretch in SHR VSMCs. This study demonstrates that mechanical stretch augments SHR VSMC proliferation through an AT/EGF receptor/ERK-dependent pathway. These findings may provide new insights into the signaling mechanisms whereby AngII exerts its growth-promoting effects on vasculature in a hypertensive state.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to mechanical stimulus  IEP 5131524mechanical stretchRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)


Additional Information