Effect of YKL-40 RNA Interference on VEGF Gene Polymorphism Expression in Atherosclerotic Mice
Abstract
Aims: To investigate the effect of YKL-40 RNA interference on VEGF gene polymorphism expression in atherosclerotic mice. Methods: After the atherosclerosis models in mice were built, the mice were divided into three groups including control group, negative control group and observation group, which were separately given to normal saline, negative virus (5 × 107 TU) and YKL-40 RNA interference lentivirus. Then the whole blood DNA was extracted and genotyped in each group of mice and the expression of VEGF in each group of mice was detected by PCR, while the expression level of inflammatory factors in each group of mice was detected by ELISA. Meanwhile, the aortas of mice in each group were pathologically analyzed and the atherosclerosis of mice was detected. Results: Compared with the control group, the VEGF content in both the virus negative control group and the observation group was significantly increased(P<0.05). The detection rates of CC genotype and C allele at rs699947 of VEGF gene in the observation group were significantly higher than those in the control group and the virus negative control group, and the difference was statistically significant. There were no significant changes for the expression of HDL-C, LDL-C, TC and TG in mice of each group(P>0.05). Moreover, the levels of Lp-PLA2 and MCP-1 in the negative control group were significantly increased (P < 0.05), while those in the observation group were significantly decreased (P < 0.05) compared to that in control group. What’s more, the histomorphology of the observation group was significantly different from that of the control group and the virus negative control group. The thickness of the fibrous cap of the as plaque was significantly higher than that of the control group and the virus negative control group, but the plaque area and fat content were significantly lower than that of the control group and the virus negative control group and the NC group. Besides, there was no significant difference in lipid content, fiber cap thickness and plaque area between the control group and the virus negative control group. Conclusion: YKL-40 RNAi could improve the VEGF polymorphism, reduce the expression of LPâƒPLA2 and MCPâƒ1, and significantly inhibit the occurrence and development of atherosclerosis, which was expected to provide a new target for the prevention and treatment of atherosclerosis.
References
[2] Zhao ZZ & Jiang ZS, New progress in several hot areas of basic research on atherosclerosis in China. Chinese Journal of arteriosclerosis. 2019; 27: 10.
[3] Egaña-Gorroño L, Chinnasamy P, Casimiro I, Almonte VM, Parikh D, Oliveira-Paula GH, et al. Allograft inflammatory factor-1 supports macrophage survival and efferocytosis and limits necrosis in atherosclerotic plaques. Atherosclerosis. 2019; 289: 184-194.
[4] Wang K, & Cui JS, Research progress of inflammatory factor markers in patients with atherosclerosis Medical review. 2021; 27: 5.
[5] Dabravolski SA, & Khotina VA. The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets. 2022; 23.
[6] Melincovici CS, Boşca AB, Şuşman S, Mărginean M, Mihu C, Istrate M, et al. Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis. Rom J Morphol Embryol. 2018; 59: 455-467.
[7] Cai YH & Guan J, Research Progress on the relationship between vascular endothelial growth factor gene polymorphism and coronary heart disease Electronic Journal of Integrated Chinese and Western Medicine on cardiovascular disease. 2018; 6: 2.
[8] Dam MN, Axelsson A, Ruwald MH, Dalsgaard M, Steffensen R, Iversen K, et al. The inflammatory biomarker YKL-40 decreases stepwise after exercise stress test. Cardiovasc Endocrinol. 2016; 5: 21-27.
[9] Libby P. The changing landscape of atherosclerosis. Nature. 592: 524-533.
[10] Soehnlein O, & Libby P. Targeting inflammation in atherosclerosis-from experimental insights to the clinic. Nature Reviews Drug Discovery.
[11] Li AY, & Zhao XF, Association between vascular endothelial growth factor-2578 gene polymorphism and lower extremity atherosclerosis Jilin Medical Science. 2021.
[12] Moulton KS, Vakili K, Zurakowski D, Soliman M, Butterfield C, Sylvin E, et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci U S A. 2003; 100: 4736-4741.
[13] Kalayi NS, Ziaee S, Boroumand MA, Sotudeh AM, Pourgholi L, & Jalali A. The impact of vascular endothelial growth factor +405 C/G polymorphism on long-term outcome and severity of coronary artery disease. J Clin Lab Anal. 2017; 31.
[14] Ma WQ, Wang Y, Han XQ, Zhu Y, & Liu NF. Association of genetic polymorphisms in vascular endothelial growth factor with susceptibility to coronary artery disease: a meta-analysis. BMC Med Genet. 2018; 19: 108.
Copyright (c) 2022 Jiamin Niu
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors submitting to USP journals agree to publish their manuscript under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0) where authors agree to allow third parties to share their work (copy, distribute, transmit) and to adapt it, under the condition that the authors are given credit, and that in the event of reuse or distribution, the terms of this license are made clear
Authors retain copyright of their work, with first publication rights (online and print) granted to Universe Scientific Publishing or the owner of the journal in question.