Gingerol Inhibits Serum-Induced Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by Suppressing p38 MAPK Activation

Jain, Manish; Singh, Ankita; Singh, Vishal; Maurya, Preeti; Barthwal, Manoj Kumar

doi:10.1177/1074248415598003

Cited by 17 publications

(10 citation statements)

References 57 publications

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“…We next investigated potential mechanisms that mediate the suppressive effect of 5-MTP on IL-1β-induced VSMC proliferation. Mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK1/2 participate in mediating VSMC proliferation regulated by various mediators 27 28 29 30 31 and in the pathogenesis of neointimal hyperplasia after vascular injury 32 33 . Thus, we examined the involvement of MAPK signaling pathways in IL-1β-induced VSMC proliferation.…”

Section: Resultsmentioning

confidence: 99%

A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury

et al. 2016

Sci Rep

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5-Methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, was recently shown to suppress inflammatory mediator-induced cancer cell proliferation and migration. However, the role of 5-MTP in vascular disease is unknown. In this study, we investigated whether 5-MTP protects against vascular remodeling following arterial injury. Measurements of serum 5-MTP levels in healthy subjects and patients with coronary artery disease (CAD) showed that serum 5-MTP concentrations were inversely correlated with CAD. To test the role of 5-MTP in occlusive vascular disease, we subjected mice to a carotid artery ligation model of neointima formation and treated mice with vehicle or 5-MTP. Compared with vehicle-treated mice, 5-MTP significantly reduced intimal thickening by 40% 4 weeks after ligation. BrdU incorporation assays revealed that 5-MTP significantly reduced VSMC proliferation both in vivo and in vitro. Furthermore, 5-MTP reduced endothelial loss and detachment, ICAM-1 and VCAM-1 expressions, and inflammatory cell infiltration in the ligated arterial wall, suggesting attenuation of endothelial dysfunction. Signaling pathway analysis indicated that 5-MTP mediated its effects predominantly via suppressing p38 MAPK signaling in endothelial and VSMCs. Our data demonstrate a novel vascular protective function of 5-MTP against arterial injury-induced intimal hyperplasia. 5-MTP might be a therapeutic target for preventing and/or treating vascular remodeling.

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Section: Resultsmentioning

confidence: 99%

A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury

et al. 2016

Sci Rep

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“…Bright-field images were acquired using an Olympus BX51 microscope equipped with a ×20 objective. Circumferences of the external and internal elastic lamina (EEL, IEL) and the lumen were traced on the stained sections ( 44 ). The intimal area was determined by subtracting the lumen area from the area circumscribed by the IEL traced on stained sections, whereas medial area was defined as the area between an EEL and an IEL ( 45 ).…”

Section: Methodsmentioning

confidence: 99%

Integrin α9 regulates smooth muscle cell phenotype switching and vascular remodeling

Jain¹,

Doddapattar²,

Kawa³

et al. 2021

JCI Insight

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“…To assess endothelium dependent relaxation, aortic rings were washed and subsequently pre-constricted with a submaximal concentration of PE (inducing 60–80% of maximal vasoconstriction). Rings were then exposed to cumulative doses of Acetylcholine (Ach; 3 nM–300 μM; Jain et al, 2016 ). Relaxation response to Ach was expressed as the net decrease in force (ΔmN) generated by submaximal PE.…”

Section: Methodsmentioning

confidence: 99%

Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment

et al. 2016

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Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this “intra-arterial” PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions.Aim: We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis.Methods and Results: Visudyne® (100, 200, and 500 ng/ml) was perfused for 5–30 min in atherosclerotic aorta isolated from ApoE−/− mice. The fluorescence Intensity (FI) after 15 min of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 ± 2.5) to 10 min (FI-23.3 ± 3.0) and 15 min (FI-42.9 ± 3.4) before reaching saturation at 30 min (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm2, irradiance-334 mW/cm2) was applied immediately after Visudyne® perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL; 2.5 ± 1.6, 41.3 ± 15.3, 58.9 ± 6%), mainly plaque macrophages (immunostaining; 0.3 ± 0.2, 37.6 ± 6.4, 45.3 ± 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm2. Limited apoptosis was observed in the medial wall (0.5 ± 0.2, 8.5 ± 4.7, 15.3 ± 12.7%). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram).Conclusion: We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short-time and therefore validated the feasibility of local intravascular administration of photosensitizer. Intra-arterial Visudyne®-PDT preferentially affected plaque macrophages and may therefore alter the dynamic progression of plaque development.

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Gingerol Inhibits Serum-Induced Vascular Smooth Muscle Cell Proliferation and Injury-Induced Neointimal Hyperplasia by Suppressing p38 MAPK Activation

Cited by 17 publications

References 57 publications

A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury

A Novel Protective Function of 5-Methoxytryptophan in Vascular Injury

Integrin α9 regulates smooth muscle cell phenotype switching and vascular remodeling

Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment

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