journal article·2024-11-12Open access

The two coin sides of bacterial extracellular membrane nanovesicles: atherosclerosis trigger or remedy

Konstantin A. Lusta, Alexey V. Churov, Dmitry F. Beloyartsev, Alexander L. Golovyuk, Arthur A. Lee, Vasily N. Sukhorukov, Alexander N. Orekhov

Discover Nano· Volume 19· Issue 1

Abstract

Among the numerous driving forces that cause the atherosclerotic cardiovascular disease (ASCVD), pathogenic bacterial extracellular membrane nanovesicles (BEMNs) containing toxins and virulence factors appear to be the key trigger of inflammation and atherogenesis, the major processes involved in the pathogenesis of ASCVD. Since BEMNs are the carriers of nanosized biomolecules to distant sites, they are now being considered as a novel drug delivery system. Nowadays, many therapeutic strategies are used to treat ASCVD. However, the conventional anti-atherosclerotic therapies are not effective enough. This primarily due to the inefficiency of non-targeted drug delivery systems to tissue affected areas, which, in turn, leads to numerous side effects, as well as faulty pharmacokinetics. In this regard, nanomedicine methods using nanoparticles (NPs) as targeted drug delivery vehicles proved to be extremely useful. Bioengineered BEMNs equipped with disease-specific ligand moieties and loaded with corresponding drugs represent a promising tool in nanomedicine, which can be used as a novel drug delivery system for a successful therapy of ASCVD. In this review, we outline the involvement of pathogenic BEMNs in the triggering of ASCVD, the conventional therapeutic strategies for the treatment of ASCVD, and the recent trends in nanomedicine using BEMNs and NPs as a vehicle for targeted drug delivery.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Bacterial Infections and Vaccines · Infective Endocarditis Diagnosis and Management · Streptococcal Infections and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (100+)

Show source-provided references
1. Poznyak AV, Bharadwaj D, Prasad G, Grechko AV, Sazonova MA, Orekhov AN. Anti-inflammatory therapy for atherosclerosis: focusing on cytokines. Int J Mol Sci. 2021;22(13):7061–72. https://doi.org/10.3390/ijms22137061.10.3390/ijms22137061 ↗
2. Lusta KA, Summerhill VI, Khotina VA, Sukhorukov VN, Glanz VY, Orekhov AN. The role of bacterial extracellular membrane nanovesicles in atherosclerosis: unraveling a potential trigger. Curr Atheroscler Rep. 2024;26(7):289–304. https://doi.org/10.1007/s11883-024-01206-6.10.1007/s11883-024-01206-6 ↗
3. Lusta KA, Poznyak AV, Litvinova L, Poggio P, Orekhov AN, Melnichenko AA. Involvement of bacterial extracellular membrane nanovesicles in infectious diseases and their application in medicine. Pharmaceutics. 2022;14(12):2597–618. https://doi.org/10.3390/pharmaceutics14122597.10.3390/pharmaceutics14122597 ↗
4. Lusta KA. Bacterial outer membrane nanovesicles: structure, biogenesis, functions, and application in biotechnology and medicine (Review). Prikl Biokhim Mikrobiol. 2015;51(5):443–52.
5. Soult MC, Lonergan NE, Shah B, Kim WK, Britt LD, Sullivan CJ. Outer membrane vesicles from pathogenic bacteria initiate an inflammatory response in human endothelial cells. J Surg Res. 2013;184(1):458–66. https://doi.org/10.1016/j.jss.2013.05.035.10.1016/j.jss.2013.05.035 ↗
6. Xu K, Wang L, Liu J. Bacterial outer membrane vesicles and their functionalization as vehicles for bioimaging, diagnosis and therapy. Mater Adv. 2022;3:7185–97. https://doi.org/10.1039/D2MA00420H.10.1039/D2MA00420H ↗
7. Chen S, Lei Q, Zou X, Ma D. The role and mechanisms of gram-negative bacterial outer membrane vesicles in inflammatory diseases. Front Immunol. 2023;14:1157813–33. https://doi.org/10.3389/fimmu.2023.1157813.10.3389/fimmu.2023.1157813 ↗
8. Yu YJ, Wang XH, Fan GC. Versatile effects of bacterium-released membrane vesicles on mammalian cells and infectious/inflammatory diseases. Acta Pharmacol Sin. 2018;39(4):514–33. https://doi.org/10.1038/aps.2017.82.10.1038/aps.2017.82 ↗
9. Wang N, Zhou F, Chen C, Luo H, Guo J, Wang W, Yang J, Li L. Role of Outer Membrane Vesicles from Helicobacter pylori in atherosclerosis. Front Cell Dev Biol. 2021;9:673993–4006. https://doi.org/10.3389/fcell.2021.673993.10.3389/fcell.2021.673993 ↗
10. Fleetwood AJ, Lee MKS, Singleton W, Achuthan A, Lee MC, O’Brien-Simpson NM, et al. Metabolic remodeling, inflammasome activation, and pyroptosis in macrophages stimulated by Porphyromonas gingivalis and its outer membrane vesicles. Front Cell Infect Microbiol. 2017;7:351–66. https://doi.org/10.3389/fcimb.2017.00351.10.3389/fcimb.2017.00351 ↗
11. Bitto NJ, Baker PJ, Dowling JK, Wray-McCann G, De Paoli A, Tran LS, Leung PL, Stacey KJ, Mansell A, Masters SL, Ferrero RL. Membrane vesicles from pseudomonas aeruginosa activate the noncanonical inflammasome through caspase-5 in human monocytes. Immunol Cell Biol. 2018;96(10):1120–30. https://doi.org/10.1111/imcb.12190.10.1111/imcb.12190 ↗
12. Cecil JD, O’Brien-Simpson NM, Lenzo JC, Holden JA, Singleton W, Perez-Gonzalez A, et al. Outer membrane vesicles prime and activate macrophage Inflammasomes and cytokine secretion In Vitro and In Vivo. Front Immunol. 2017;8:1017–39. https://doi.org/10.3389/fimmu.2017.01017.10.3389/fimmu.2017.01017 ↗
13. Deo P, Chow SH, Han ML, Speir M, Huang C, Schittenhelm RB, et al. Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation. Nat Microbiol. 2020;5(11):1418–27. https://doi.org/10.1038/s41564-020-0773-2.10.1038/s41564-020-0773-2 ↗
14. Endo S, Goldsmith HL, Karino T. Flow patterns and preferred sites of atherosclerotic lesions in the human aorta - I. Aortic arch Biorheology. 2014;51(4–5):239–55. https://doi.org/10.3233/BIR-14005.10.3233/BIR-14005 ↗
15. Sivapalaratnam S, Motazacker MM, Maiwald S, Hovingh GK, Kastelein JJ, Levi M, Trip MD, Dallinga-Thie GM. Genome-wide association studies in atherosclerosis. Curr Atheroscler Rep. 2011;13(3):225–32. https://doi.org/10.1007/s11883-011-0173-4.10.1007/s11883-011-0173-4 ↗
16. Orekhov AN. Mechanisms of atherogenesis and development of anti-atherosclerotic therapy. Curr Pharm Des. 2015;21(9):1103–6. https://doi.org/10.2174/138161282109150103213605.10.2174/138161282109150103213605 ↗
17. Lusta KA, Poznyak AV, Sukhorukov VN, Eremin II, Nadelyaeva II, Orekhov AN. Hypotheses on atherogenesis triggering: does the infectious nature of atherosclerosis development have a substruction? Cells. 2023;12(5):707–24. https://doi.org/10.3390/cells12050707.10.3390/cells12050707 ↗
18. Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, et al. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Front Pharmacol. 2021;11:613780–91. https://doi.org/10.3389/fphar.2020.613780.10.3389/fphar.2020.613780 ↗
19. Chan YH, Ramji DPA. perspective on targeting inflammation and cytokine actions in atherosclerosis. Future Med Chem. 2020;12:613–26. https://doi.org/10.4155/fmc-2019-0301.10.4155/fmc-2019-0301 ↗
20. Ridker PM, Lüscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J. 2014;14:1782–91. https://doi.org/10.1093/eurheartj/ehu203.10.1093/eurheartj/ehu203 ↗
21. Nasonov EL, Popkova TV. Atherosclerosis: perspectives of anti-inflammatory therapy. Ter Arkh. 2018;11:4–12. https://doi.org/10.26442/terarkh201890514-12.10.26442/terarkh201890514-12 ↗
22. Chistiakov DA, Melnichenko AA, Grechko AV, Myasoedova VA, Orekhov AN. Potential of anti-inflammatory agents for treatment of atherosclerosis. Exp Mol Pathol. 2018;104(2):114–24. https://doi.org/10.1016/j.yexmp.2018.01.008.10.1016/j.yexmp.2018.01.008 ↗
23. Gluba-Brzózka A, Franczyk B, Rysz-Górzyńska M, Ławiński J, Rysz J. Emerging anti-atherosclerotic therapies. Int J Mol Sci. 2021;22(22):12109–41. https://doi.org/10.3390/ijms222212109.10.3390/ijms222212109 ↗
24. Cheng J, Huang H, Chen Y, Wu R. Nanomedicine for diagnosis and treatment of atherosclerosis. Adv Sci (Weinh). 2023;10(36):e2304294. https://doi.org/10.1002/advs.202304294.10.1002/advs.202304294 ↗
25. Perera B, Wu Y, Nguyen NT, Ta HT. Advances in drug delivery to atherosclerosis: Investigating the efficiency of different nanomaterials employed for different type of drugs. Mater Today Bio. 2023;22:100767–87. https://doi.org/10.1016/j.mtbio.2023.100767.10.1016/j.mtbio.2023.100767 ↗
26. Ou LC, Zhong S, Ou JS, Tian JW. Application of targeted therapy strategies with nanomedicine delivery for atherosclerosis. Acta Pharmacol Sin. 2021;42(1):10–7. https://doi.org/10.1038/s41401-020-0436-0.10.1038/s41401-020-0436-0 ↗
27. Hossaini Nasr S, Huang X. Nanotechnology for targeted therapy of atherosclerosis. Front Pharmacol. 2021;12:755569–81. https://doi.org/10.3389/fphar.2021.755569.10.3389/fphar.2021.755569 ↗
28. Luo T, Zhang Z, Xu J, Liu H, Cai L, Huang G, et al. Atherosclerosis treatment with nanoagent: potential targets, stimulus signals and drug delivery mechanisms. Front Bioeng Biotechnol. 2023;11:1205751–72. https://doi.org/10.3389/fbioe.2023.1205751.10.3389/fbioe.2023.1205751 ↗
29. Tang TT, Wang B, Lv LL, Liu BC. Extracellular vesicle-based Nanotherapeutics: emerging frontiers in anti-inflammatory therapy. Theranostics. 2020;10(18):8111–29. https://doi.org/10.7150/thno.47865.10.7150/thno.47865 ↗
30. Kostyushev D, Kostyusheva A, Brezgin S, Smirnov V, Volchkova E, Lukashev A, et al. Gene editing by extracellular vesicles. Int J Mol Sci. 2020;21(19):7362–98. https://doi.org/10.3390/ijms21197362.10.3390/ijms21197362 ↗
31. Liu H, Pietersz G, Peter K, Wang X. Nanobiotechnology approaches for cardiovascular diseases: site-specific targeting of drugs and NPs for atherothrombosis. J Nanobiotechnology. 2022;20(1):75–98. https://doi.org/10.1186/s12951-022-01279-y.10.1186/s12951-022-01279-y ↗
32. Collins SM, Brown AC. Bacterial outer membrane vesicles as antibiotic delivery vehicles. Front Immunol. 2021;12:733064–77. https://doi.org/10.3389/fimmu.2021.733064.10.3389/fimmu.2021.733064 ↗
33. Li R, Liu Q. Engineered bacterial outer membrane vesicles as multifunctional delivery platforms. Front Mater. 2020;7:202–20. https://doi.org/10.3389/fmats.2020.00202.10.3389/fmats.2020.00202 ↗
34. Aytar Çelik P, Erdogan-Gover K, Barut D, Enuh BM, Amasya G, Sengel-Türk CT, et al. Bacterial membrane vesicles as smart drug delivery and carrier systems: a new nanosystems tool for current anticancer and antimicrobial therapy. Pharmaceutics. 2023;15(4):1052–93. https://doi.org/10.3390/pharmaceutics15041052.10.3390/pharmaceutics15041052 ↗
35. Wang S, Gao J, Wang Z. Outer membrane vesicles for vaccination and targeted drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2019;11(2):e1523. https://doi.org/10.1002/wnan.1523.10.1002/wnan.1523 ↗
36. Lieberman LA. Outer membrane vesicles: a bacterial-derived vaccination system. Front Microbiol. 2022;21(13):1029146. https://doi.org/10.3389/fmicb.2022.1029146.10.3389/fmicb.2022.1029146 ↗
37. Ahmed AAQ, Besio R, Xiao L, Forlino A. Outer membrane vesicles (OMVs) as biomedical tools and their relevance as immune-modulating agents against H. pylori infections: current status and future prospects. Int J Mol Sci. 2023;24(10):8542. https://doi.org/10.3390/ijms24108542.10.3390/ijms24108542 ↗
38. Roy M, Roy A, Rustagi S, Pandey N. An overview of nanomaterial applications in pharmacology. Biomed Res Int. 2023;2023:4838043–66. https://doi.org/10.1155/2023/4838043.10.1155/2023/4838043 ↗
39. Chen H, Zhou M, Zeng Y, Lv Z, Wang P, Han L. Recent advances in biomedical applications of bacterial outer membrane vesicles. J Mater Chem B. 2022;10(37):7384–96. https://doi.org/10.1039/d2tb00683a.10.1039/d2tb00683a ↗
40. Elsharkasy OM, Nordin JZ, Hagey DW, de Jong OG, Schiffelers RM, Andaloussi SE, et al. Extracellular vesicles as drug delivery systems: Why and how? Adv Drug Deliv Rev. 2020;159:332–43. https://doi.org/10.1016/j.addr.2020.04.004.10.1016/j.addr.2020.04.004 ↗
41. Zhang LY, Yang X, Wang SB, Chen H, Pan HY, Hu ZM. Membrane derived vesicles as biomimetic carriers for targeted drug delivery system. Curr Top Med Chem. 2020;20(27):2472–92. https://doi.org/10.2174/1568026620666200922113054.10.2174/1568026620666200922113054 ↗
42. Catapano A, Pirillo A, Norata GD. Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials. Br J Pharmacol. 2017;174(22):3973–85. https://doi.org/10.1111/bph.13805.10.1111/bph.13805 ↗
43. Jiang H, Zhou Y, Nabavi SM, Sahebkar A, Little PJ, Xu S, et al. Mechanisms of oxidized LDL-mediated endothelial dysfunction and its consequences for the development of atherosclerosis. Front Cardiovasc Med. 2022;1(9):925923. https://doi.org/10.3389/fcvm.2022.925923-34.10.3389/fcvm.2022.925923-34 ↗
44. Azemawah V, Movahed MR, Centuori P, Penaflor R, Riel PL, Situ S, et al. State of the art comprehensive review of individual statins, their differences, pharmacology, and clinical implications. Cardiovasc Drugs Ther. 2019;33(5):625–39. https://doi.org/10.1007/s10557-019-06904-x.10.1007/s10557-019-06904-x ↗
45. Phan BA, Dayspring TD, Toth pp PP. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415–27. https://doi.org/10.2147/VHRM.S33664.10.2147/VHRM.S33664 ↗
46. Lim GB. Bempedoic acid prevents cardiovascular events in statin-intolerant patients. Nat Rev Cardiol. 2023;20(5):285. https://doi.org/10.1038/s41569-023-00863-5.10.1038/s41569-023-00863-5 ↗
47. Zeman M, Vecka M, Perlík F, Hromádka R, Staňková B, Tvrzická E, et al. Niacin in the treatment of hyperlipidemias in light of new clinical trials: has niacin lost its place? Med Sci Monit. 2015;21:2156–62. https://doi.org/10.12659/MSM.893619.10.12659/MSM.893619 ↗
48. Katzmann JL, Gouni-Berthold I, Laufs U. PCSK9 inhibition: insights from clinical trials and future prospects. Front Physiol. 2020;11:595819–37. https://doi.org/10.3389/fphys.2020.595819.10.3389/fphys.2020.595819 ↗
49. Day EA, Ford RJ, Smith BK, Houde VP, Stypa S, Rehal S, et al. Salsalate reduces atherosclerosis through AMPKβ1 in mice. Mol Metab. 2021;53:101321–30. https://doi.org/10.1016/j.molmet.2021.101321.10.1016/j.molmet.2021.101321 ↗
50. Welsh P, Grassia G, Botha S, Sattar N, Maffia P. Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect? Br J Pharmacol. 2017;174(22):3898–913. https://doi.org/10.1111/bph.13818.10.1111/bph.13818 ↗
51. Ridker PM. Anticytokine agents: targeting interleukin signaling pathways for the treatment of atherothrombosis. Circ Res. 2019;124(3):437–50. https://doi.org/10.1161/CIRCRESAHA.118.313129.10.1161/CIRCRESAHA.118.313129 ↗
52. Roman YM, Hernandez AV, White CM. The role of suppressing inflammation in the treatment of atherosclerotic cardiovascular disease. Ann Pharmacother. 2020;54(10):1021–9. https://doi.org/10.1177/1060028020922994.10.1177/1060028020922994 ↗
53. Wang Y, Liu X, Shi H, Yu Y, Yu Y, Li M, et al. NLRP3 inflammasome, an immune-inflammatory target in pathogenesis and treatment of cardiovascular diseases. Clin Transl Med. 2020;10(1):91–106. https://doi.org/10.1002/ctm2.13.10.1002/ctm2.13 ↗
54. Lutgens E, Atzler D, Döring Y, Duchene J, Steffens S, Weber C. Immunotherapy for cardiovascular disease. Eur Heart J. 2019;40(48):3937–46. https://doi.org/10.1093/eurheartj/ehz283.10.1093/eurheartj/ehz283 ↗
55. Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) immunotherapy. Cold Spring Harb Perspect Biol. 2018;10(8):a028456–71. https://doi.org/10.1101/cshperspect.a028456.10.1101/cshperspect.a028456 ↗
56. Bami S, Vagrecha A, Soberman D, Badawi M, Cannone D, Lipton JM, et al. The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2020;67(11):e28581. https://doi.org/10.1002/pbc.28581.10.1002/pbc.28581 ↗
57. Pandey A, Goyal M. Methotrexate: CIRTified for preventing atherosclerotic events? J R Coll Physicians Edinb. 2019;49(2):136–8. https://doi.org/10.4997/JRCPE.2019.211.10.4997/JRCPE.2019.211 ↗
58. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak pp PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244–79. https://doi.org/10.1016/j.pharmthera.2007.10.001.10.1016/j.pharmthera.2007.10.001 ↗
59. Zhang FS, He QZ, Qin CH, Little PJ, Weng JP, Xu SW. Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review. Acta Pharmacol Sin. 2022;43(9):2173–90. https://doi.org/10.1038/s41401-021-00835-w.10.1038/s41401-021-00835-w ↗
60. López-Castejón G, Pelegrín P. Current status of inflammasome blockers as anti-inflammatory drugs. Expert Opin Investig Drugs. 2012;21(7):995–1007. https://doi.org/10.1517/13543784.2012.690032.10.1517/13543784.2012.690032 ↗
61. Zhang X, Wang Z, Zheng Y, Yu Q, Zeng M, Bai L, et al. Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review). Int J Mol Med. 2023;51(4):35–56. https://doi.org/10.3892/ijmm.2023.5238.10.3892/ijmm.2023.5238 ↗
62. Chan CKW, Zhang L, Cheng CK, Yang H, Huang Y, Tian, et al. Recent advances in managing atherosclerosis via nanomedicine. Small. 2018. https://doi.org/10.1002/smll.201702793.10.1002/smll.201702793 ↗
63. Di Fusco SA, Maggioni AP, Scicchitano P, Zuin M, D’Elia E, Colivicchi F. Lipoprotein (a), inflammation, and atherosclerosis. J Clin Med. 2023;12(7):2529–43. https://doi.org/10.3390/jcm12072529.10.3390/jcm12072529 ↗
64. Kim MA, Kim CJ, Seo JB, Chung WY, Kim SH, Zo JH, et al. The effect of aspirin on C-reactive protein in hypertensive patients. Clin Exp Hypertens. 2011;33(1):47–52. https://doi.org/10.3109/10641963.2010.503302.10.3109/10641963.2010.503302 ↗
65. Martinez BK, White CM. The emerging role of inflammation in cardiovascular disease. Ann Pharmacother. 2018;52(8):801–9. https://doi.org/10.1177/1060028018765939.10.1177/1060028018765939 ↗
66. Lüscher TF, Landmesser U, von Eckardstein A, Fogelman AM. High-density lipoprotein: vascular protective effects, dysfunction, and potential as therapeutic target. Circ Res. 2014;114(1):171–82. https://doi.org/10.1161/CIRCRESAHA.114.300935.10.1161/CIRCRESAHA.114.300935 ↗
67. Chyu KY, Shah PK. HDL/ApoA-1 infusion and ApoA-1 gene therapy in atherosclerosis. Front Pharmacol. 2015;6:187–96. https://doi.org/10.3389/fphar.2015.00187.10.3389/fphar.2015.00187 ↗
68. Poznyak AV, Sukhorukov VN, Eremin II, Nadelyaeva II, Gutyrchik NA, Orekhov AN. HDL-based therapy: vascular protection at all stages. Biomedicines. 2023;11(3):711–27. https://doi.org/10.3390/biomedicines11030711.10.3390/biomedicines11030711 ↗
69. Summerhill VI, Grechko AV, Yet SF, Sobenin IA, Orekhov AN. The atherogenic role of circulating modified lipids in atherosclerosis. Int J Mol Sci. 2019;20(14):3561–75. https://doi.org/10.3390/ijms20143561.10.3390/ijms20143561 ↗
70. Mezentsev A, Bezsonov E, Kashirskikh D, Baig MS, Eid AH, Orekhov A. Proatherogenic sialidases and desialylated lipoproteins: 35 years of research and current state from bench to bedside. Biomedicines. 2021;9(6):600–17. https://doi.org/10.3390/biomedicines9060600.10.3390/biomedicines9060600 ↗
71. Sobenin IA, Markin AM, Glanz VY, Markina YV, Wu WK, Myasoedova VA, et al. Prospects for the use of sialidase inhibitors in anti-atherosclerotic therapy. Curr Med Chem. 2021;28(12):2438–50. https://doi.org/10.2174/0929867327666200831133912.10.2174/0929867327666200831133912 ↗
72. Bowles WHD, Gloster TM. Sialidase and Sialyltransferase inhibitors: targeting pathogenicity and disease. Front Mol Biosci. 2021;8:705133–43. https://doi.org/10.3389/fmolb.2021.705133.10.3389/fmolb.2021.705133 ↗
73. Singh SK, Agrawal A. Functionality of C-reactive protein for atheroprotection. Front Immunol. 2019;10:1655–63. https://doi.org/10.3389/fimmu.2019.01655.10.3389/fimmu.2019.01655 ↗
74. Burtenshaw D, Kitching M, Redmond EM, Megson IL, Cahill PA. Reactive oxygen species (ros), intimal thickening, and subclinical atherosclerotic disease. Front Cardiovasc Med. 2019;6:89–107. https://doi.org/10.3389/fcvm.2019.00089.10.3389/fcvm.2019.00089 ↗
75. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97(10):2499–574. https://doi.org/10.1007/s00204-023-03562-9.10.1007/s00204-023-03562-9 ↗
76. Batty M, Bennett MR, Yu E. The role of oxidative stress in atherosclerosis. Cells. 2022;11(23):3843–63. https://doi.org/10.3390/cells11233843.10.3390/cells11233843 ↗
77. Porrini C, Ramarao N, Dr Tran SL., NO and Mr. Toxic - the versatile role of nitric oxide. Biol Chem. 2020;401(5):547–72. https://doi.org/10.1515/hsz-2019-0368.10.1515/hsz-2019-0368 ↗
78. Raddino R, Caretta G, Teli M, Bonadei I, Robba D, Zanini G, Madureri A, Nodari S, Dei CL. Nitric oxide and cardiovascular risk factors. Heart Int. 2007;3(1):18. https://doi.org/10.4081/hi.2007.18.10.4081/hi.2007.18 ↗
79. Förstermann U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch. 2010;459(6):923–39. https://doi.org/10.1007/s00424-010-0808-2.10.1007/s00424-010-0808-2 ↗
80. Zhang B, Tian M, Zhu J, Zhu A. Global research trends in atherosclerosis-related NF-κB: a bibliometric analysis from 2000 to 2021 and suggestions for future research. Ann Transl Med. 2023;11(2):57. https://doi.org/10.21037/atm-22-6145.10.21037/atm-22-6145 ↗
81. Cheng W, Cui C, Liu G, Ye C, Shao F, Bagchi AK, et al. NF-κB, A potential therapeutic target in cardiovascular diseases. Cardiovasc Drugs Ther. 2023;37(3):571–84. https://doi.org/10.1007/s10557-022-07362-8.10.1007/s10557-022-07362-8 ↗
82. Patzelt J, Verschoor A, Langer HF. Platelets and the complement cascade in atherosclerosis. Front Physiol. 2015;2:49–58. https://doi.org/10.3389/fphys.2015.00049.10.3389/fphys.2015.00049 ↗
83. Harris CL, Pouw RB, Kavanagh D, Sun R, Ricklin D. Developments in anti-complement therapy; from disease to clinical trial. Mol Immunol. 2018;102:89–119. https://doi.org/10.1016/j.molimm.2018.06.008.10.1016/j.molimm.2018.06.008 ↗
84. Harris CL. Expanding horizons in complement drug discovery: challenges and emerging strategies. Semin Immunopathol. 2018;40(1):125–40. https://doi.org/10.1007/s00281-017-0655-8.10.1007/s00281-017-0655-8 ↗
85. Landmesser U, Poller W, Tsimikas S, Most P, Paneni F, Lüscher TF. From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases. Eur Heart J. 2020;41(40):3884–99. https://doi.org/10.1093/eurheartj/ehaa229.10.1093/eurheartj/ehaa229 ↗
86. Mäkinen P, Ruotsalainen AK, Ylä-Herttuala S. Nucleic acid-based therapies for atherosclerosis. Curr Atheroscler Rep. 2020;22(2):10–8. https://doi.org/10.1007/s11883-020-0826-2.10.1007/s11883-020-0826-2 ↗
87. Lu Y, Thavarajah T, Gu W, Cai J, Xu Q. Impact of miRNA in atherosclerosis. Arterioscler Thromb Vasc Biol. 2018;38(9):e159–70. https://doi.org/10.1161/ATVBAHA.118.310227.10.1161/ATVBAHA.118.310227 ↗
88. Huang X, Li A, Xu P, Yu Y, Li S, Hu L, et al. Current and prospective strategies for advancing the targeted delivery of CRISPR/Cas system via extracellular vesicles. J Nanobiotechnology. 2023;21(1):184–209. https://doi.org/10.1186/s12951-023-01952-w.10.1186/s12951-023-01952-w ↗
89. Suárez-Rivero JM, Pastor-Maldonado CJ, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Talaverón-Rey M, et al. From mitochondria to atherosclerosis: the inflammation path. Biomedicines. 2021;9(3):258. https://doi.org/10.3390/biomedicines9030258.10.3390/biomedicines9030258 ↗
90. Sandhir R, Halder A, Sunkaria A. Mitochondria as a centrally positioned hub in the innate immune response. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1090–7. https://doi.org/10.1016/j.bbadis.2016.10.020.10.1016/j.bbadis.2016.10.020 ↗
91. Li D, Yang S, Xing Y, Pan L, Zhao R, Zhao Y, et al. Novel insights and current evidence for mechanisms of atherosclerosis: mitochondrial dynamics as a potential therapeutic target. Front Cell Dev Biol. 2021;9:673839–55. https://doi.org/10.3389/fcell.2021.673839.10.3389/fcell.2021.673839 ↗
92. Orekhov AN, Poznyak AV, Sobenin IA, Nikifirov NN, Ivanova EA. Mitochondrion as a selective target for the treatment of atherosclerosis: role of mitochondrial dna mutations and defective mitophagy in the pathogenesis of atherosclerosis and chronic inflammation. Curr Neuropharmacol. 2020;18(11):1064–75. https://doi.org/10.2174/1570159X17666191118125018.10.2174/1570159X17666191118125018 ↗
93. Sazonova MA, Ryzhkova AI, Sinyov VV, Galitsyna EV, Melnichenko AA, Demakova NA, et al. Mitochondrial genome mutations associated with myocardial infarction. Dis Markers. 2018;2018:9749457–63. https://doi.org/10.1155/2018/9749457.10.1155/2018/9749457 ↗
94. Qiang L, Hu J, Tian M, Li Y, Ren C, Deng Y, Jiang Y. Extracellular vesicles from Helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles in atherosclerosis. Helicobacter. 2022;27(2):e12877. https://doi.org/10.1111/hel.12877.10.1111/hel.12877 ↗
95. Ouimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport. Circ Res. 2019;124(10):1505–18. https://doi.org/10.1161/CIRCRESAHA.119.312617.10.1161/CIRCRESAHA.119.312617 ↗
96. Malekmohammad K, Bezsonov EE, Rafieian-Kopaei M. Role of lipid accumulation and inflammation in atherosclerosis: focus on molecular and cellular mechanisms. Front Cardiovasc Med. 2021;8:707529. https://doi.org/10.3389/fcvm.2021.707529.10.3389/fcvm.2021.707529 ↗
97. Yang S, Xia YP, Luo XY, Chen SL, Li BW, Ye ZM, et al. Exosomal CagA derived from Helicobacter pylori-infected gastric epithelial cells induces macrophage foam cell formation and promotes atherosclerosis. J Mol Cell Cardiol. 2019;135:40–51. https://doi.org/10.1016/j.yjmcc.2019.07.011.10.1016/j.yjmcc.2019.07.011 ↗
98. Krisch LM, Posselt G, Hammerl P, Wessler S. CagA phosphorylation in helicobacter pylori-Infected B cells is mediated by the nonreceptor tyrosine kinases of the Src and Abl families. Infect Immun. 2016;84(9):2671–80. https://doi.org/10.1128/IAI.00349-16.10.1128/IAI.00349-16 ↗
99. Mueller D, Tegtmeyer N, Brandt S, Yamaoka Y, De Poire E, Sgouras D, et al. c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in western and east Asian helicobacter pylori strains. J Clin Invest. 2012;122(4):1553–66. https://doi.org/10.1172/JCI61143.10.1172/JCI61143 ↗
100. Majdalawieh A, Ro HS. PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1. Nucl Recept Signal. 2010;8:e004. https://doi.org/10.1621/nrs.08004.10.1621/nrs.08004 ↗