title: Grape seed procyanidin b2 inhibits human aortic smooth muscle cell proliferation and migration induced by advanced glycation end products.
abstract: Advanced glycation end product (AGE)-induced vascular smooth muscle cell (VSMC) proliferation is vital to the progression of diabetic vasculopathy. A grape seed procyanidin extract has been reported to possess anti-oxidative and anti-inflammatory properties and to display a significant cardiovascular protective effect, but little is know about the underlying mechanism. The objective of this present study was to determine whether GSPB2 (grape seed procyanidin B2), which is a dimeric procyanidin and more biologically active, could inhibit AGE-induced VSMC proliferation by affecting the production of ubiquitin COOH-terminal hydrolase 1 (UCH-L1), the degradation of IκB-α and nuclear translocation of NF-κB in human aortic smooth muscle cells (HASMCs). Our data show that GSPB2 preincubation markedly inhibited AGE-induced proliferation and migration of HASMCs in a dose-dependent manner and upregulated the protein level of UCH-L1. Further studies revealed that the GSPB2 pretreatment markedly attenuated the degradation of IκB-α and nuclear translocation of NF-κB by modulating ubiquitination of IκB-α in AGE-exposed HASMCs. These results collectively suggest that AGE-induced HASMC proliferation and migration was suppressed by GSPB2 through regulating UCH-L1 and ubiquitination of IκB-α. GSPB2 may therefore have therapeutic potential in preventing and treating vascular complications of diabetes mellitus.
authors: Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, Qi-Lu Hospital of Shandong University, China.
authors: Qian
authors: Q
authors: Cai
authors: Bao-ying
authors: BY
authors: Li
authors: Hai-qing
authors: HQ
authors: Gao
authors: Jian-hua
authors: JH
authors: Zhang
authors: Jun-fu
authors: JF
authors: Wang
authors: Fei
authors: F
authors: Yu
authors: Mei
authors: M
authors: Yin
authors: Zhen
authors: Z
authors: Zhang
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000009:adverse effects; D056604:Grape Seed Extract / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D017127:Glycation End Products, Advanced; D056604:Grape Seed Extract; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; C482860:UCHL1 protein, human; D000072000:NF-KappaB Inhibitor alpha; C479580:procyanidin B2; D002392:Catechin; D043222:Ubiquitin Thiolesterase