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

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.

Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats

“…Here, we show that S. minor can be effective in ameliorating the induced infarction, which could be due to the presence of different bioactive ingredients such as quercetin (Panda and Kar, 2015), kaempferol (Vishwakarma et al, 2018a), myricetin (Tiwari et al, 2009), catechin (Devika and Prince, 2008), and ellagic acid (Warpe et al, 2015). These and other flavonoids are well known to exert various beneficial effects including cardiovasculoprotective ones (Fardoun et al, 2019;Maaliki et al, 2019;Fardoun et al, 2020;Alsamri et al, 2021b;Slika et al, 2022). In particular, the cardioprotective effects of quercetin have been widely documented in both in vitro and in vivo experimental models of cardiac injury.…”

The Effects of Pro-Inflammatory and Anti-Inflammatory Agents for the Suppression of Intimal Hyperplasia: An Evidence-Based Review

“…Inflammation within the vascular wall is a hurdle, and manipulating the inflammatory cytokines and chemokines is possibly the key piece in solving the puzzle. Other than that, research related to inhibition of intimal hyperplasia has also been extensively done using various approaches, which utilized gene therapy and vector-mediated gene delivery [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ], anti-inflammatory and anti-proliferative drugs [ 57 ], compounds with anti-inflammatory actions such as plants [ 55 , 65 ], herbal medications [ 50 ], marine sources [ 52 ] and polyunsaturated fatty acids [ 56 ].…”