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AuthorFardoun M.
AuthorIratni R.
AuthorDehaini H.
AuthorEid A.
AuthorGhaddar T.
AuthorEl-Elimat T.
AuthorAlali F.
AuthorBadran A.
AuthorEid A.H.
AuthorBaydoun E.
Available date2020-04-05T10:53:20Z
Publication Date2019
Publication NameBiomolecules
ISSN2218273X
URIhttp://dx.doi.org/10.3390/biom9110716
URIhttp://hdl.handle.net/10576/13811
AbstractRemodeling of arterioles is a pivotal event in the manifestation of many inflammation-based cardio-vasculopathologies, such as hypertension. During these remodeling events, vascular smooth muscle cells (VSMCs) switch from a contractile to a synthetic phenotype. The latter is characterized by increased proliferation, migration, and invasion. Compounds with anti-inflammatory actions have been successful in attenuating this phenotypic switch. While the vast majority of studies investigating phenotypic modulation were undertaken in VSMCs isolated from large vessels, little is known about the effect of such compounds on phenotypic switch in VSMCs of microvessels (microVSMCs). We have recently characterized a novel homoisoflavonoid that we called 7-O-methylpunctatin (MP). In this study, we show that MP decreased FBS-induced cell proliferation, migration, invasion, and adhesion. MP also attenuated adhesion of THP-1 monocytes to microVSMCs, abolished FBS-induced expression of MMP-2, MMP-9, and NF-?B, as well as reduced activation of ERK1/2 and FAK. Furthermore, MP-treated VSMCs showed an increase in early (myocardin, SM-22?, SM-?) and mid-term (calponin and caldesmon) differentiation markers and a decrease in osteopontin, a protein highly expressed in synthetic VSMCs. MP also reduced transcription of cyclin D1, CDK4 but increased protein levels of p21 and p27. Taken together, these results corroborate an anti-inflammatory action of MP on human microVSMCs. Therefore, by inhibiting the synthetic phenotype of microVSMCs, MP may be a promising modulator for inflammation-induced arteriolar pathophysiology. - 2019 by the authors. Licensee MDPI, Basel, Switzerland.
SponsorFunding: This work was supported by the American University of Beirut (Grant # MPP 320133 to A.E.), University of Petra (Grant #: 5/4/2019) to A.B., E.B., and A.E., and the National Council for Scientific Research (CNRS) to M.F.
Languageen
PublisherMDPI AG
Subject7-O-methylpunctatin
SubjectArterioles
SubjectHomoisoflavonoids
SubjectInflammation
SubjectPhenotypic switch
SubjectVascular smooth muscle cells
Title7-O-methylpunctatin, a novel homoisoflavonoid, inhibits phenotypic switch of human arteriolar smooth muscle cells
TypeArticle
Issue Number11
Volume Number9


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