Exploring the Mechanism of Atherosclerosis and the Intervention of Traditional Chinese Medicine Combined with Mesenchymal Stem Cells Based on Inflammatory Targets

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Dec 4

PMID 38045166

Authors

Shibiao Sun

Feixiang Liu

Feiyan Fan

Na Chen

Xiaolong Pan

Zhihui Wei

Yunke Zhang

Affiliations

Soon will be listed here.

Abstract

Atherosclerosis (AS) is a chronic inflammatory vascular disease, which is the common pathological basis of cardiovascular and cerebrovascular diseases. The immune inflammatory response throughout the course of AS has been evidenced by studies, in which a large number of immune cells and inflammatory factors play a crucial role in the pathogenesis of AS. The inflammation related to AS is mainly mediated by inflammatory cytokines (IL-1β, IL-6, IL-18, TNF-α, hs-CRP, SAA), inflammatory enzymes (Lp-PLA2, sPLA2-IIA, MMPs), and inflammatory signaling pathways (P38 MAPK signaling pathway, NF-κB signaling pathway, TLR2/4 signaling pathway). It is involved in the pathophysiological process of AS, and the degree of inflammation measured by it can be used to evaluate the risk of progression of AS plaque instability. In recent years, traditional Chinese medicine (TCM) has shown the advantage of minimal side effects in immune regulation and has made some progress in the prevention and treatment of AS. Mesenchymal stem cells (MSCs), as self-renewal, highly differentiated, and pluripotent stem cells with anti-inflammatory properties and immune regulation, have been widely used for AS treatment. They also play an important inflammation-immune regulatory function in AS. Notably, in terms of regulating immune cells and inflammatory factors, compared with TCM and its compound, the combination therapy has obvious anti-inflammatory advantages over the use of MSCs alone. It is an important means to further improve the efficacy of AS and provides a new way for the prevention and treatment of AS.

Citing Articles

Chinese and western medicine treatment of myocardial fibrosis drugs.

Zhu Y, Zhang F, Li Z, Zhou Y, Shu Y, Ruan J Front Cardiovasc Med. 2025; 11:1477601.

PMID: 39882321 PMC: 11774883. DOI: 10.3389/fcvm.2024.1477601.

High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis.

Wang X, Li S, Liu C, Zhao J, Ren G, Zhang F J Transl Med. 2024; 22(1):967.

PMID: 39449149 PMC: 11515432. DOI: 10.1186/s12967-024-05679-6.

Unveiling TIMPs: A Systematic Review of Their Role as Biomarkers in Atherosclerosis and Coronary Artery Disease.

Aminuddin A, Samah N, Vijakumaran U, Che Roos N, Mohd Nor F, Wan Razali W Diseases. 2024; 12(8).

PMID: 39195176 PMC: 11353419. DOI: 10.3390/diseases12080177.

References

Lu C, Yang Y, Li C, Liu K, Lii C, Chen H . Andrographolide inhibits TNFα-induced ICAM-1 expression via suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression through the PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 pathways in human endothelial cells. Biochem Pharmacol. 2014; 91(1):40-50. DOI: 10.1016/j.bcp.2014.06.024. View

Shi H, Liang M, Chen W, Sun X, Wang X, Li C . Human induced pluripotent stem cell‑derived mesenchymal stem cells alleviate atherosclerosis by modulating inflammatory responses. Mol Med Rep. 2017; 17(1):1461-1468. PMC: 5780084. DOI: 10.3892/mmr.2017.8075. View

Zhao D, Tong L, Zhang L, Li H, Wan Y, Zhang T . Tanshinone II A stabilizes vulnerable plaques by suppressing RAGE signaling and NF-κB activation in apolipoprotein-E-deficient mice. Mol Med Rep. 2016; 14(6):4983-4990. PMC: 5355755. DOI: 10.3892/mmr.2016.5916. View

Kaden J, Dempfle C, Grobholz R, Tran H, Kilic R, Sarikoc A . Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis. Atherosclerosis. 2003; 170(2):205-11. DOI: 10.1016/s0021-9150(03)00284-3. View

Chen Z, Gao X, Jiao Y, Qiu Y, Wang A, Yu M . Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially the TLR4/MyD88/NF-κB Signal Pathway. Front Pharmacol. 2019; 10:850. PMC: 6677033. DOI: 10.3389/fphar.2019.00850. View

Wang G, Ji C, Wang C, Liu Z, Qu A, Wang H . Matrine ameliorates the inflammatory response and lipid metabolism in vascular smooth muscle cells through the NF-κB pathway. Exp Ther Med. 2021; 22(5):1309. PMC: 8461614. DOI: 10.3892/etm.2021.10744. View

Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J . Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation. 2002; 106(1):24-30. DOI: 10.1161/01.cir.0000020546.30940.92. View

Levkau B, Kenagy R, Karsan A, Weitkamp B, Clowes A, Ross R . Activation of metalloproteinases and their association with integrins: an auxiliary apoptotic pathway in human endothelial cells. Cell Death Differ. 2002; 9(12):1360-7. DOI: 10.1038/sj.cdd.4401106. View

Wang S, Zhou H, Feng T, Wu R, Sun X, Guan N . β-Glucan attenuates inflammatory responses in oxidized LDL-induced THP-1 cells via the p38 MAPK pathway. Nutr Metab Cardiovasc Dis. 2014; 24(3):248-55. DOI: 10.1016/j.numecd.2013.09.019. View

10.

Mehu M, Aluganti Narasimhulu C, Singla D . Inflammatory Cells in Atherosclerosis. Antioxidants (Basel). 2022; 11(2). PMC: 8868126. DOI: 10.3390/antiox11020233. View

11.

Shah P . Biomarkers of plaque instability. Curr Cardiol Rep. 2014; 16(12):547. DOI: 10.1007/s11886-014-0547-7. View

12.

He H, Yang T, Li F, Zhang L, Ling X . A novel study on the immunomodulatory effect of umbilical cord derived mesenchymal stem cells pretreated with traditional Chinese medicine Asarinin. Int Immunopharmacol. 2021; 100:108054. DOI: 10.1016/j.intimp.2021.108054. View

13.

Ridker P, Libby P, MacFadyen J, Thuren T, Ballantyne C, Fonseca F . Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Eur Heart J. 2018; 39(38):3499-3507. DOI: 10.1093/eurheartj/ehy310. View

14.

Jongstra-Bilen J, Zhang C, Wisnicki T, Li M, White-Alfred S, Ilaalagan R . Oxidized Low-Density Lipoprotein Loading of Macrophages Downregulates TLR-Induced Proinflammatory Responses in a Gene-Specific and Temporal Manner through Transcriptional Control. J Immunol. 2017; 199(6):2149-2157. DOI: 10.4049/jimmunol.1601363. View

15.

Zhang X, Ren Z, Jiang Z . EndMT-derived mesenchymal stem cells: a new therapeutic target to atherosclerosis treatment. Mol Cell Biochem. 2022; 478(4):755-765. DOI: 10.1007/s11010-022-04544-8. View

16.

Jiang W, Xu J . Immune modulation by mesenchymal stem cells. Cell Prolif. 2019; 53(1):e12712. PMC: 6985662. DOI: 10.1111/cpr.12712. View

17.

Wang Y, Song E, Bai B, Vanhoutte P . Toll-like receptors mediating vascular malfunction: Lessons from receptor subtypes. Pharmacol Ther. 2015; 158:91-100. DOI: 10.1016/j.pharmthera.2015.12.005. View

18.

Ryan S, McNicholas W, Taylor C . A critical role for p38 map kinase in NF-kappaB signaling during intermittent hypoxia/reoxygenation. Biochem Biophys Res Commun. 2007; 355(3):728-33. DOI: 10.1016/j.bbrc.2007.02.015. View

19.

Park L, Raman K, Lee K, Lu Y, Ferran Jr L, Chow W . Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med. 1998; 4(9):1025-31. DOI: 10.1038/2012. View

20.

Ridker P . Targeting Interleukin-1 and Interleukin-6: The Time Has Come to Aggressively Address Residual Inflammatory Risk. J Am Coll Cardiol. 2020; 76(15):1774-1776. DOI: 10.1016/j.jacc.2020.08.052. View