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Reply to “Overstated Claims of Efficacy and Safety. Comment On: Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181”
Open AccessArticle

Carnosine Impedes PDGF-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro and Sprout Outgrowth Ex Vivo

1
Department of Food and Nutrition, Chung-Ang University, 4726 Seodong-Daero, Daedeok-Myeon, Anseong 17546, Korea
2
Department of Ophthalmology, College of Medicine, Chung-Ang University, Heukseok-ro, Dongjak-gu, Seoul 84, Korea
3
Department of Urology, Chungbuk National University, Cheongju 361-763, Korea
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(9), 2697; https://doi.org/10.3390/nu12092697
Received: 26 June 2020 / Revised: 31 August 2020 / Accepted: 1 September 2020 / Published: 3 September 2020
(This article belongs to the Section Phytochemicals and Human Health)
Carnosine, a naturally producing dipeptide, exhibits various beneficial effects. However, the possible role of carnosine in vascular disorders associated with pathological conditions, including proliferation and migration of vascular smooth muscle cells (VSMCs), largely remains unrevealed. Here, we investigated the regulatory role and mechanism of carnosine in platelet-derived growth factor (PDGF)-induced VSMCs. Carnosine inhibited the proliferation of PDGF-induced VSMCs without any cytotoxic effects. Carnosine treatment also induced G1-phase cell cycle arrest by causing a p21WAF1-mediated reduction in the expression of both cyclin-dependent kinases (CDKs) and cyclins in PDGF-treated VSMCs. Carnosine treatment suppressed c-Jun N-terminal kinase (JNK) phosphorylation in PDGF-stimulated signaling. Additionally, carnosine significantly prevented the migration of VSMCs exposed to PDGF. Carnosine abolished matrix metalloproteinase (MMP)-9 activity via reduced transcriptional binding activity of NF-κB, Sp-1, and AP-1 motifs in PDGF-treated VSMCs. Moreover, using aortic assay ex vivo, it was observed that carnosine addition attenuated PDGF-stimulated sprout outgrowth of VSMCs. Taken together, these results demonstrated that carnosine impeded the proliferation and migration of PDGF-stimulated VSMCs by regulating cell cycle machinery, JNK signaling, and transcription factor-mediated MMP-9 activity as well as prevented ex vivo sprout outgrowth of blood vessels. Thus, carnosine may be a potential candidate for preventing vascular proliferative disease. View Full-Text
Keywords: carnosine; vascular smooth muscle cells; platelet-derived growth factor; proliferation; migration; aortic ring ex vivo carnosine; vascular smooth muscle cells; platelet-derived growth factor; proliferation; migration; aortic ring ex vivo
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Hwang, B.; Song, J.-H.; Park, S.L.; Kim, J.T.; Kim, W.-J.; Moon, S.-K. Carnosine Impedes PDGF-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells In Vitro and Sprout Outgrowth Ex Vivo. Nutrients 2020, 12, 2697.

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