Liraglutide blocks the proliferation, migration and phenotypic switching of Homocysteine (Hcy)-induced vascular smooth muscle cells (VSMCs) by suppressing proprotein convertase subtilisin kexin9 (PCSK9)/ low-density lipoprotein receptor (LDLR)

References

• Kosar F, Sincer I, Aksoy Y, et al. Elevated plasma homocysteine levels in patients with isolated coronary artery ectasia. Coron Artery Dis. 2006;17(1):23–27.
   PubMed Web of Science ®Google Scholar
• Wang F, Sui X, Xu N, et al. The relationship between plasma homocysteine levels and MTHFR gene variation, age, and sex in Northeast China. Niger J Clin Pract. 2019;22:380–385.
   PubMed Web of Science ®Google Scholar
• Zhao LP, You T, Chan SP, et al. Adropin is associated with hyperhomocysteine and coronary atherosclerosis. Exp Ther Med. 2016;11(3):1065–1070.
   PubMed Web of Science ®Google Scholar
• Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011;17(11):1410–1422.
   PubMed Web of Science ®Google Scholar
• Tabas I, Garcia-Cardena G, Gk O. Recent insights into the cellular biology of atherosclerosis. J Cell Biol. 2015;209(1):13–22.
   PubMed Web of Science ®Google Scholar
• Cheng Q, Zhang M, Zhang M, et al. Long non-coding RNA LOC285194 regulates vascular smooth muscle cell apoptosis in atherosclerosis. Bioengineered. 2020;11(1):53–60.
   PubMed Web of Science ®Google Scholar
• Zhang B, Hao Z, Zhou W, et al. Formononetin protects against ox-LDL-induced endothelial dysfunction by activating PPAR-γ signaling based on network pharmacology and experimental validation. Bioengineered. 2021;12(1):4887–4898.
   PubMed Web of Science ®Google Scholar
• Li Z, Xu C, Sun D. MicroRNA-488 serves as a diagnostic marker for atherosclerosis and regulates the biological behavior of vascular smooth muscle cells. Bioengineered. 2021;12(1):4092–4099.
   PubMed Web of Science ®Google Scholar
• Udhaya Kumar S, Thirumal Kumar D, Bithia R, et al. Analysis of differentially expressed genes and molecular pathways in familial hypercholesterolemia involved in atherosclerosis: a systematic and bioinformatics approach. Front Genet. 2020;11:734.
   PubMed Web of Science ®Google Scholar
• von Essen M, Rahikainen R, Oksala N, et al. Talin and vinculin are downregulated in atherosclerotic plaque; tampere vascular study. Atherosclerosis. 2016;255:43–53.
   PubMed Web of Science ®Google Scholar
• Holven KB, Narverud I, Lindvig HW, et al. Subjects with familial hypercholesterolemia are characterized by an inflammatory phenotype despite long-term intensive cholesterol lowering treatment. Atherosclerosis. 2014;233(2):561–567.
   PubMed Web of Science ®Google Scholar
• Monaco C, Sm G, TJ N, et al. Toll-like receptor-2 mediates inflammation and matrix degradation in human atherosclerosis. Circulation. 2009;120(24):2462–2469.
   PubMed Web of Science ®Google Scholar
• Cena H, Chiovato L, Nappi RE. Obesity, polycystic ovary syndrome, and infertility: a new avenue for GLP-1 receptor agonists. J Clin Endocrinol Metab. 2020;105(8):e2695–e2709.
   PubMed Web of Science ®Google Scholar
• Cheng KC, Li YX, Shieh PC, et al. Liraglutide activates glucagon-like peptide 1 receptor to attenuate hyperglycemia through endogenous beta-endorphin in diabetic rats. Pharmaceuticals (Basel). 2020;13(11):407.
   Google Scholar
• Yang SH, Xu RX, Cui CJ, et al. Liraglutide downregulates hepatic LDL receptor and PCSK9 expression in HepG2 cells and db/db mice through a HNF-1a dependent mechanism. Cardiovasc Diabetol. 2018;17(1):48.
   PubMed Web of Science ®Google Scholar
• Tang ZH, Peng J, Ren Z, et al. New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-kappaB pathway. Atherosclerosis. 2017;262:113–122.
   PubMed Web of Science ®Google Scholar
• Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50(Suppl):S172–177.
   PubMed Web of Science ®Google Scholar
• Lin H, Ni T, Zhang J, et al. Knockdown of Herp alleviates hyperhomocysteinemia mediated atherosclerosis through the inhibition of vascular smooth muscle cell phenotype switching. Int J Cardiol. 2018;269:242–249.
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–408.
   PubMed Web of Science ®Google Scholar
• Iovino M, Messana T, De Pergola G, et al. Brain angiotensinergic regulation of the immune system: implications for cardiovascular and neuroendocrine responses. Endocr Metab Immune Disord Drug Targets. 2020;20(1):15–24.
   PubMed Web of Science ®Google Scholar
• Basatemur GL, Jorgensen HF, Clarke MCH, et al. Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol. 2019;16:727–744.
   PubMed Web of Science ®Google Scholar
• Lund A, Knop FK, Vilsboll T. Emerging GLP-1 receptor agonists. Expert Opin Emerg Drugs. 2011;16(4):607–618.
   PubMed Web of Science ®Google Scholar
• Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al., Emerging Risk Factors C. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364:829–841.
   PubMed Web of Science ®Google Scholar
• Mak KH, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I investigators. global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries. J Am Coll Cardiol. 1997;30(1):171–179.
   PubMed Web of Science ®Google Scholar
• Caruso I, Cignarelli A, Giorgino F. Heterogeneity and similarities in GLP-1 receptor agonist cardiovascular outcomes trials. Trends Endocrinol Metab. 2019;30(9):578–589.
   PubMed Web of Science ®Google Scholar
• Durgin BG, Straub AC. Redox control of vascular smooth muscle cell function and plasticity. Lab Invest. 2018;98(10):1254–1262.
   PubMed Web of Science ®Google Scholar
• Rudijanto A. The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones. 2007;39:86–93.
   PubMedGoogle Scholar
• Nagayama K, Kyotani Y, Zhao J, et al. Exendin-4 prevents vascular smooth muscle cell proliferation and migration by angiotensin II via the inhibition of ERK1/2 and JNK signaling pathways. PLoS One. 2015;10(9):e0137960.
   PubMed Web of Science ®Google Scholar
• Yang HH, Xu YX, Chen JY, et al. N-Butylidenephthalide inhibits the phenotypic switch of VSMCs through activation of AMPK and prevents stenosis in an arteriovenous fistula rat model. Int J Mol Sci. 2020;21(19):7403.
   Web of Science ®Google Scholar
• Furmanik M, Chatrou M, Van Gorp R, et al. Reactive oxygen-forming Nox5 links vascular smooth muscle cell phenotypic switching and extracellular vesicle-mediated vascular calcification. Circ Res. 2020;127(7):911–927.
   PubMed Web of Science ®Google Scholar
• Safaeian L, Vaseghi G, Jabari H, et al. Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, promotes angiogenesis in vitro. Can J Physiol Pharmacol. 2019;97(5):352–358.
   PubMed Web of Science ®Google Scholar
• Pelletier L, Rebouissou S, Vignjevic D, et al. HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines. BMC Cancer. 2011;11(1):427.
   PubMed Web of Science ®Google Scholar
• Sucajtys-Szulc E, Szolkiewicz M, Swierczynski J, et al. Up-regulation of Hnf1α gene expression in the liver of rats with experimentally induced chronic renal failure - A possible link between circulating PCSK9 and triacylglycerol concentrations. Atherosclerosis. 2016;248:17–26.
   PubMed Web of Science ®Google Scholar
• Urban D, Poss J, Bohm M, et al. Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol. 2013;62(16):1401–1408.
   PubMed Web of Science ®Google Scholar
• Wang Y, Ma M, Wang JA, et al. Targeting proprotein convertase subtilisin/kexin type 9 in mice and monkeys. Curr Opin Lipidol. 2019;30(2):154–155.
   PubMed Web of Science ®Google Scholar
• Grune J, Meyborg H, Bezhaeva T, et al. PCSK9 regulates the chemokine receptor CCR2 on monocytes. Biochem Biophys Res Commun. 2017;485(2):312–318.
   PubMed Web of Science ®Google Scholar
• Xiang Q, Liu W, Zeng J, et al. Effect of PCSK9 on vascular smooth muscle cell functions: a new player in atherosclerosis. Curr Med Chem. 2021;28. DOI:10.2174/0929867328666210531150302
   Web of Science ®Google Scholar
• Kwon HJ, Lagace TA, McNutt MC, et al. Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A. 2008;105(6):1820–1825.
   PubMed Web of Science ®Google Scholar
• Seidah NG, Awan Z, Chrétien M, et al. PCSK9: a key modulator of cardiovascular health. Circ Res. 2014;114(6):1022–1036.
   PubMed Web of Science ®Google Scholar
• Liu X, Qin Z, Liu C, et al. and soluble epoxide hydrolase synergistically mediate homocysteine-induced inflammation in vascular smooth muscle cells. Vascul Pharmacol. 2019;120:106544.
   PubMed Web of Science ®Google Scholar
• Ren JL, Hou YL, Ni XQ, et al. Intermedin 1-53 ameliorates homocysteine-promoted atherosclerotic calcification by inhibiting endoplasmic reticulum stress. J Cardiovasc Pharmacol Ther. 2020;25(3):251–264.
   PubMed Web of Science ®Google Scholar