Abstract
The proliferation-promoting effect of neuropeptide Y (NPY) always functions in low-serum-cultured vascular smooth muscle cells (VSMCs), and the phenotypic switch of VSMCs is regulated by concentrations of serum. Whether the property of the NPY proliferative effect in VSMCs relies on phenotype of VSMCs is unclear. We aimed to explore the role of NPY on proliferation of different VSMC phenotypes in the pathogenesis of atherosclerosis. By stimulating A10 cells with 200 nM NPY in 0.5 or 10% serum, 3H-thymidine and 5-ethynyl-2′-deoxyuridine (EdU) and CCK8 measurements were used to detect VSMC proliferation. RT-PCR and Flow cytometry were performed to detect the factors involved in different properties of the NPY proliferative effect in VSMCs. Instead of facilitating proliferation, NPY had no significant effect on the growth of VSMCs when cultured in 10% serum (VSMCs stayed at synthetic states). The underlying mechanism may be involved in down-regulation of Y1 receptor (P < 0.05 vs. Vehicle) and up-regulation of Geminin (P < 0.05 vs. Vehicle) in 10% serum-cultured VSMCs co-incubated with 200 nM NPY. Besides, modulation of Geminin was effectively blocked by the Y1 receptor antagonist. The stimulation of NPY on proliferation of VSMCs could be a double-edged sword in the development of atherosclerosis and thus provides new knowledge for therapy of atherosclerosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Dzau VJ, Braun-Dullaeus RC, Sedding DG (2002) Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med 8:1249–1256. doi:10.1038/nm1102-1249
Legein B, Temmerman L, Biessen EA, Lutgens E (2013) Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci 70:3847–3869. doi:10.1007/s00018-013-1289-1
Schachter M (1997) Vascular smooth muscle cell migration, atherosclerosis, and calcium channel blockers. Int J Cardiol 62(Suppl 2):S85–S90
Hao H, Gabbiani G, Bochaton-Piallat ML (2003) Arterial smooth muscle cell heterogeneity: implications for atherosclerosis and restenosis development. Arterioscler Thromb Vasc Biol 23:1510–1520. doi:10.1161/01.ATV.0000090130.85752.ED
Rensen SS, Doevendans PA, van Eys GJ (2007) Regulation and characteristics of vascular smooth muscle cell phenotypic diversity. Neth Heart J 15:100–108
Lobaugh LA, Blackshear PJ (1990) Neuropeptide Y stimulation of myosin light chain phosphorylation in cultured aortic smooth muscle cells. J Biol Chem 265:18393–18399
Herring N (2015) Autonomic control of the heart: going beyond the classical neurotransmitters. Exp Physiol 100:354–358. doi:10.1113/expphysiol.2014.080184
Pons J, Kitlinska J, Jacques D, Perreault C, Nader M, Everhart L, Zhang Y, Zukowska Z (2008) Interactions of multiple signaling pathways in neuropeptide Y-mediated bimodal vascular smooth muscle cell growth. Can J Physiol Pharmacol 86:438–448. doi:10.1139/y08-054
Zhu P, Sun W, Zhang C, Song Z, Lin S (2016) The role of neuropeptide Y in the pathophysiology of atherosclerotic cardiovascular disease. Int J Cardiol 220:235–241. doi:10.1016/j.ijcard.2016.06.138
Zukowska-Grojec Z, Karwatowska-Prokopczuk E, Fisher TA, Ji H (1998) Mechanisms of vascular growth-promoting effects of neuropeptide Y: role of its inducible receptors. Regul Pept 75–76:231–238
Zhang P, Qi YX, Yao QP, Chen XH, Wang GL, Shen BR, Han Y, Gao LZ, Jiang ZL (2015) Neuropeptide Y stimulates proliferation and migration of vascular smooth muscle cells from pregnancy hypertensive rats via Y1 and Y5 receptors. PLoS ONE 10:e0131124. doi:10.1371/journal.pone.0131124
Crnkovic S, Egemnazarov B, Jain P, Seay U, Gattinger N, Marsh LM, Balint Z, Kovacs G, Ghanim B, Klepetko W, Schermuly RT, Weissmann N, Olschewski A, Kwapiszewska G (2014) NPY/Y(1) receptor-mediated vasoconstrictory and proliferative effects in pulmonary hypertension. Br J Pharmacol 171:3895–3907. doi:10.1111/bph.12751
Reusch P, Wagdy H, Reusch R, Wilson E, Ives HE (1996) Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. Circ Res 79:1046–1053
Wilson E, Mai Q, Sudhir K, Weiss RH, Ives HE (1993) Mechanical strain induces growth of vascular smooth muscle cells via autocrine action of PDGF. J Cell Biol 123:741–747
Chistiakov DA, Orekhov AN, Bobryshev YV (2015) Vascular smooth muscle cell in atherosclerosis. Acta Physiol (Oxf) 214:33–50. doi:10.1111/apha.12466
Bina RB, Hill N, Brem AS (1998) Effect of serum on vascular smooth muscle function. Life Sci 62:1195–1201
Zhang Y, Jiang Z, Li L, Zhou Y, Song Z, Shu M (2014) Geminin interference facilitates vascular smooth muscle cell proliferation by upregulation of CDK-1. Cardiovasc Drugs Ther 28:407–414. doi:10.1007/s10557-014-6550-9
Zhou Y, Shi W, Luo H, Yue R, Wang Z, Wang W, Liu L, Wang WE, Wang H, Zeng C (2015) Inhibitory effect of D1-like dopamine receptors on neuropeptide Y-induced proliferation in vascular smooth muscle cells. Hypertens Res 38:807–812. doi:10.1038/hr.2015.84
Yulyaningsih E, Zhang L, Herzog H, Sainsbury A (2011) NPY receptors as potential targets for anti-obesity drug development. Br J Pharmacol 163:1170–1202. doi:10.1111/j.1476-5381.2011.01363.x
Suchyta M, Miotto B, McGarry TJ (2015) An inactive geminin mutant that binds cdt1. Genes (Basel) 6:252–266. doi:10.3390/genes6020252
Karamitros D, Kotantaki P, Lygerou Z, Veiga-Fernandes H, Pachnis V, Kioussis D, Taraviras S (2010) Life without geminin. Cell Cycle 9:3181–3185. doi:10.4161/cc.9.16.12554
Lagraauw HM, Westra MM, Bot M, Wezel A, van Santbrink PJ, Pasterkamp G, Biessen EA, Kuiper J, Bot I (2014) Vascular neuropeptide Y contributes to atherosclerotic plaque progression and perivascular mast cell activation. Atherosclerosis 235:196–203. doi:10.1016/j.atherosclerosis.2014.04.025
Son YH, Jeong YT, Lee KA, Choi KH, Kim SM, Rhim BY, Kim K (2008) Roles of MAPK and NF-kappaB in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells. J Cardiovasc Pharmacol 51:71–77. doi:10.1097/FJC.0b013e31815bd23d
Saleh Al-Shehabi T, Iratni R, Eid AH (2016) Anti-atherosclerotic plants which modulate the phenotype of vascular smooth muscle cells. Phytomedicine 23:1068–1081. doi:10.1016/j.phymed.2015.10.016
Pons J, Kitlinska J, Ji H, Lee EW, Zukowska Z (2003) Mitogenic actions of neuropeptide Y in vascular smooth muscle cells: synergetic interactions with the beta-adrenergic system. Can J Physiol Pharmacol 81:177–185. doi:10.1139/y02-166
Shalaw FG, Slimani S, Kolopp-Sarda MN, Marchand M, Faure G, Stoltz JF, Muller S (2006) Effect of cyclic stretching and foetal bovine serum (FBS) on proliferation and extra cellular matrix synthesis of fibroblast. Biomed Mater Eng 16:S137–S144
Murphy LO, Cluck MW, Lovas S, Otvos F, Murphy RF, Schally AV, Permert J, Larsson J, Knezetic JA, Adrian TE (2001) Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions. Br J Cancer 84:926–935. doi:10.1054/bjoc.2001.1698
Funding
This study was supported by the National Natural Science Foundation of China (No. 81570396).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
We declare there was no commercial, proprietary, or financial interest conflict in the products or companies described in this article.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Jiang, Zq., Zhou, Yl., Chen, X. et al. Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin. Mol Cell Biochem 433, 205–211 (2017). https://doi.org/10.1007/s11010-017-3028-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-017-3028-7