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Open AccessArticle

7-O-Methylpunctatin, a Novel Homoisoflavonoid, Inhibits Phenotypic Switch of Human Arteriolar Smooth Muscle Cells

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Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
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Department of Biology, College of Science, United Arab Emirates University, P.O. Box 15551, Al-Ain, UAE
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Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
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Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
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Department of Chemistry, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut, Lebanon
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Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
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College of Pharmacy, Qatar University, Doha P.O. Box 2713, Qatar
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Department of Nutrition, University of Petra, Amman, P.O. Box 961343, Amman 11196, Jordan
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Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha P.O. Box 2713, Qatar
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Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 716; https://doi.org/10.3390/biom9110716
Received: 6 August 2019 / Revised: 9 October 2019 / Accepted: 9 October 2019 / Published: 8 November 2019
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. View Full-Text
Keywords: vascular smooth muscle cells; inflammation; phenotypic switch; homoisoflavonoids; 7-O-methylpunctatin; arterioles vascular smooth muscle cells; inflammation; phenotypic switch; homoisoflavonoids; 7-O-methylpunctatin; arterioles
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Fardoun, M.; Iratni, R.; Dehaini, H.; Eid, A.; Ghaddar, T.; El-Elimat, T.; Alali, F.; Badran, A.; Eid, A.H.; Baydoun, E. 7-O-Methylpunctatin, a Novel Homoisoflavonoid, Inhibits Phenotypic Switch of Human Arteriolar Smooth Muscle Cells. Biomolecules 2019, 9, 716.

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