7-O-methylpunctatin, a novel homoisoflavonoid, inhibits phenotypic switch of human arteriolar smooth muscle cells

Manal Fardoun, Rabah Iratni, Hassan Dehaini, Assaad Eid, Tarek Ghaddar, Tamam El-Elimat, Feras Alali, Adnan Badran, Ali H. Eid, Elias Baydoun

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Remodeling 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-κB, as well as reduced activation of ERK1/2 and FAK. Furthermore, MP-treated VSMCs showed an increase in early (myocardin, SM-22α, SM-α) 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.

Original languageEnglish
Article number716
JournalBiomolecules
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2019

Keywords

  • 7-O-methylpunctatin
  • Arterioles
  • Homoisoflavonoids
  • Inflammation
  • Phenotypic switch
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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