Korean Chemical Engineering Research

The Korean Institute of Chemical Engineers (한국화학공학회)
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Current Status and Application Prospects of Anti-Atherosclerotic Active Biomaterials

항동맥경화 활성 바이오소재 개발 연구 동향 및 활용 전망

  • Seunghee Kim (Department of Biotechnology, Sangmyung University) ;
  • Jeongho Lee (Department of Biotechnology, Sangmyung University) ;
  • Hah Young Yoo (Department of Biotechnology, Sangmyung University)
  • 김승희 (상명대학교 생명공학과) ;
  • 이정호 (상명대학교 생명공학과) ;
  • 유하영 (상명대학교 생명공학과)
  • Received : 2024.01.25
  • Accepted : 2024.02.15
  • Published : 2024.05.01
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Abstract

Atherosclerosis, a disease with high morbidity and mortality worldwide, is a chronic inflammatory disease that is a major cause of cardiovascular diseases such as stroke and myocardial infarction. Atherosclerosis is characterized by the accumulation of lipid deposits in the arteries, forming atheromas. This leads to the narrowing of the arteries and thrombosis. Recently, the need to develop bio-derived anti-atherosclerotic materials has been highlighted with concerns about the side effects of synthetic therapeutics. Accordingly, related research (such as the discovery of biomaterials for the improvement and treatment of atherosclerosis and the identification of mechanisms) has been actively conducted. Biomaterials including polysaccharides, polyphenols, and coenzyme Q10 have been reported to inhibit or delay symptoms by modulating factors involved in the development of atherosclerosis. For biomaterials with superior activity, in vivo anti-atherosclerotic activity has been confirmed. In this review, the pathogenesis of atherosclerosis was investigated, and the current status and application prospects of biomaterials with anti-atherosclerotic activity were proposed.

전세계적으로 발병 및 사망률이 높은 동맥경화증은 뇌졸중, 심근경색 등 심혈관질환의 주요 병증의 원인인 만성 염증성 질환이다. 동맥경화증은 지질 침착으로 인해 죽종(atheroma)이 형성되고, 혈전증이 유발되면서 관련 증상이 발생한다. 동맥경화증의 합성 치료제의 부작용 우려로 인해 생물 유래 항동맥경화 소재 개발의 필요성이 강조되고 있다. 이에 따라 동맥경화증의 개선 및 치료를 위한 바이오소재의 발굴 및 기전 규명 등 관련 연구가 활발히 수행되고 있다. 주로 동맥경화증 발병 관련 인자들을 조절하여 증상을 억제하거나 지연시키는 바이오소재들이 연구되고 있으며, 대표적으로 다당류, 폴리페놀, 코엔자임 Q10이 해당된다. 우수한 활성을 가진 바이오소재의 경우에는 생체 내(동물 모델)에서의 항동맥경화증 활성이 확인되었다. 본고에서는 동맥경화증의 발병 기전을 살펴보고, 항동맥경화증 활성이 보고된 바이오소재의 연구 동향 및 활용 전망을 제시하고자 한다.

Keywords

Acknowledgement

본 연구는 2023학년도 상명대학교 교내연구비를 지원받아 수행하였음.

References

  1. Mc Namara, K., Alzubaidi, H. and Jackson, J. K., "Cardiovascular Disease as a Leading Cause of Death: How Are Pharmacists Getting Involved?," Integr. Pharm. Res. Pract., 8, 1-11(2019).
  2. Stewart, J., Manmathan, G. and Wilkinson, P., "Primary Prevention of Cardiovascular Disease: A Review of Contemporary Guidance and Literature," Jrsm Cardiovasc. Dis., 6, 1-9(2017).
  3. Kim, J. M., Lee, W. S. and Kim, J., "Therapeutic Strategy for Atherosclerosis Based on Bone-vascular Axis Hypothesis," Pharmacol. Ther., 206, 107436(2020).
  4. Steenman, M. and Lande, G., "Cardiac Aging and Heart Disease in Humans," Biophys. Rev., 9(2), 131-137(2017). https://doi.org/10.1007/s12551-017-0255-9
  5. Mach, F., Ray, K. K., Wiklund, O., Corsini, A., Catapano, A. L., Bruckert, E., De Backer, G., Hegele, R. A., Hovingh, G.K. and Jacobson, T.A., "Adverse Effects of Statin Therapy: Perception vs. the Evidence-focus on Glucose Homeostasis, Cognitive, Renal and Hepatic Function, Haemorrhagic Stroke and Cataract," Eur. Heart J., 39(27), 2526-2539(2018).
  6. Volobueva, A., Zhang, D., Grechko, A. V. and Orekhov, A. N., "Foam Cell Formation and Cholesterol Trafficking and Metabolism Disturbances in Atherosclerosis," Cor Vasa, 61, 48-55(2018).
  7. Michel, C. C. and Curry, F. E., "Microvascular Permeability," Physiol. Rev., 79, 703-761(1999).
  8. Jang, E., Robert, J., Rohrer, L., von Eckardstein, A. and Lee, W. L., "Transendothelial Transport of Lipoproteins," Atherosclerosis, 315, 111-125(2020).
  9. Vos, D. Y. and van de Sluis, B., "Function of the Endolysosomal Network in Cholesterol Homeostasis and Metabolic-associated Fatty Liver Disease (MAFLD)," Mol. Metab., 50, 101146(2021).
  10. Levitan, I., Volkov, S. and Subbaiah, P. V., "Oxidized LDL: Diversity, Patterns of Recognition, and Pathophysiology," Antioxid. Redox Signal., 13(1), 39-75(2010).
  11. Galimberti, F., Casula, M. and Olmastroni, E., "Apolipoprotein B Compared with Low-density Lipoprotein Cholesterol in the Atherosclerotic Cardiovascular Diseases Risk Assessment," Pharmacol. Res., 195, 106873(2023).
  12. Ahmadi, A., Panahi, Y., Johnston, T. P. and Sahebkar, A., "Antidiabetic Drugs and Oxidized Low-density Lipoprotein: A Review of Anti-atherosclerotic Mechanisms," Pharmacol. Res., 172, 105819 (2021).
  13. Nachtigal, P., Semecky, V., Kopecky, M., Gojova, A., Solichova, D., Zdansky, P. and Zadak, Z., "Application of Stereological Methods for the Quantification of VCAM-1 and ICAM-1 Expression in Early Stages of Rabbit Atherogenesis," Pathol. Res. Pract., 200(3), 219-229(2004). https://doi.org/10.1016/j.prp.2004.02.008
  14. Lin, J., Kakkar, V. and Lu, X., "Impact of MCP-1 in Atherosclerosis," Curr. Pharm. Des., 20(28), 4580-4588(2014). https://doi.org/10.2174/1381612820666140522115801
  15. De Paoli, F., Staels, B. and Chinetti-Gbaguidi, G., "Macrophage Phenotypes and Their Modulation in Atherosclerosis," Circ. J., 78(8), 1775-1781(2014). https://doi.org/10.1253/circj.CJ-14-0621
  16. Hofnagel, O., Luechtenborg, B., Weissen-Plenz, G. and Robenek, H., "Statins and Foam Cell Formation: Impact on LDL Oxidation and Uptake of Oxidized Lipoproteins via Scavenger Receptors," Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1771(9), 1117-1124(2007).
  17. Chistiakov, D. A., Melnichenko, A. A., Myasoedova, V. A., Grechko, A. V. and Orekhov, A. N., "Mechanisms of Foam Cell Formation in Atherosclerosis," J. Mol. Med., 95(11), 1153-1165(2017). https://doi.org/10.1007/s00109-017-1575-8
  18. Williams, K. J. and Tabas, I., "Lipoprotein Retention-and Clues for Atheroma Regression," Arterioscler. Thromb. Vasc. Biol., 25(8), 1536-1540(2005). https://doi.org/10.1161/01.ATV.0000174795.62387.d3
  19. Vlacil, A. K., Schuett, J., Schieffer, B. and Grote, K., "Variety Matters: Diverse Functions of Monocyte Subtypes in Vascular Inflammation and Atherogenesis," Vasc. Pharmacol., 113, 9-19 (2019).
  20. Nording, H., Baron, L. and Langer, H. F., "Platelets as Therapeutic Targets to Prevent Atherosclerosis," Atherosclerosis, 307, 97-108(2020).
  21. Mitra, S., Deshmukh, A., Sachdeva, R., Lu, J. and Mehta, J. L., "Oxidized Low-density Lipoprotein and Atherosclerosis Implications in Antioxidant Therapy," Am. J. Med. Sci., 342(2), 135-142(2011). https://doi.org/10.1097/MAJ.0b013e318224a147
  22. Brown, R. A., Shantsila, E., Varma, C. and Lip, G. Y., "Current Understanding of Atherogenesis," Am. J. Med., 130(3), 268-282 (2017). https://doi.org/10.1016/j.amjmed.2016.10.022
  23. Maguire, E. M., Pearce, S. W. and Xiao, Q., "Foam Cell Formation: A New Target for Fighting Atherosclerosis and Cardiovascular Disease," Vascul. Pharmacol., 112, 54-71(2019).
  24. Yan, P., Xia, C., Duan, C., Li, S. and Mei, Z., "Biological Characteristics of Foam Cell Formation in Smooth Muscle Cells Derived From Bone Marrow Stem Cells," Int. J. Biol. Sci., 7(7), 937(2011).
  25. Sorokin, V., Vickneson, K., Kofidis, T., Woo, C. C., Lin, X. Y., Foo, R. and Shanahan, C. M., "Role of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation," Front. immunol., 11, 599415(2020).
  26. Sanson, M., Auge, N., Vindis, C., Muller, C., Bando, Y., Thiers, J. C., Marachet, M. A., Zarkovic, K., Sawa, Y., Salvayre, R. and Negre-Salvayre, A., "Oxidized Low-density Lipoproteins Trigger Endoplasmic Reticulum Stress in Vascular Cells: Prevention by Oxygen-regulated Protein 150 Expression," Circ. Res., 104(3), 328-336(2009).
  27. Cheng, H., Cheng, Q., Bao, X., Luo, Y., Zhou, Y., Li, Y., Hua, Q., Liu, W., Tang, S. Feng, D. and Luo, Z., "Over-activation of NMDA Receptors Promotes ABCA1 Degradation and Foam Cell Formation," Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1865(10), 158778(2020).
  28. Teng, N., Maghzal, G. J., Talib, J., Rashid, I., Lau, A. K. and Stocker, R., "The Roles of Myeloperoxidase in Coronary Artery Disease and Its Potential Implication in Plaque Rupture," Redox Rep., 22(2), 51-73(2017). https://doi.org/10.1080/13510002.2016.1256119
  29. Bentzon, J. F., Otsuka, F., Virmani, R. and Falk, E., "Mechanisms of Plaque Formation and Rupture," Circ. Res., 114(12), 1852-1866(2014). https://doi.org/10.1161/CIRCRESAHA.114.302721
  30. Watson, M. G., Byrne, H. M., Macaskill, C. and Myerscough, M. R., "A Two-phase Model of Early Fibrous Cap Formation in Atherosclerosis," J. Theor. Biol., 456, 123-136(2018).
  31. Glass, C. K. and Witztum, J. L. Atherosclerosis: the Road Ahead. Cell, 104(4), 503-516(2001).
  32. Huang, N. F., Okogbaa, J., Lee, J. C., Jha, A., Zaitseva, T. S., Paukshto, M. V., Sun, J. S., Punjya, N., Fuller, G. G. and Cooke, J. P., "The Modulation of Endothelial Cell Morphology, Function, and Survival Using Anisotropic Nanofibrillar Collagen Scaffolds," Biomaterials, 34(16), 4038-4047(2013). https://doi.org/10.1016/j.biomaterials.2013.02.036
  33. Cameron, J. N., Mehta, O. H., Michail, M., Chan, J., Nicholls, S. J., Bennett, M. R. and Brown, A. J., "Exploring the Relationship Between Biomechanical Stresses and Coronary Atherosclerosis," Atherosclerosis, 302, 43-51(2020).
  34. Chien, S., "Molecular and Mechanical Bases of Focal Lipid Accumulation in Arterial Wall," Prog. Biophys. Mol., 83(2), 131-151(2003). https://doi.org/10.1016/S0079-6107(03)00053-1
  35. Chiu, J. J., Lee, P. L., Chen, C. N., Lee, C. I., Chang, S. F., Chen, L. J., Lien, S. C., Ko., Y. C., Usami, S. and Chien, S., "Shear Stress Increases ICAM-1 and Decreases VCAM-1 and E-selectin Expressions Induced by Tumor Necrosis Factor-α in Endothelial Cells," Arter. Thromb. Vasc. Biol., 24(1), 73-79(2004). https://doi.org/10.1161/01.ATV.0000106321.63667.24
  36. Zhou, M., Yu, Y., Chen, R., Liu, X., Hu, Y., Ma, Z., Gao, L., Jian, W. and Wang, L. "Wall Shear Stress and Its Role in Atherosclerosis," Front. Cardiovasc. Med., 10, 1083547(2023).
  37. Williams, H., Johnson, J. L., Jackson, C. L., White, S. J. and George, S. J., "MMP-7 Mediates Cleavage of N-cadherin and Promotes Smooth Muscle Cell Apoptosis," Cardiovasc. Res., 87(1), 137-146(2010). https://doi.org/10.1093/cvr/cvq042
  38. Newby, A. C., "Proteinases and Plaque Rupture: Unblocking the Road to Translation," Curr. Opin. Lipidol., 25(5), 358-366(2014).
  39. Barascuk, N., Skjot-Arkil, H., Register, T. C., Larsen, L., Byrjalsen, I., Christiansen, C. and Karsdal, M. A., "Human Macrophage Foam Cells Degrade Atherosclerotic Plaques Through Cathepsin K Mediated Processes," BMC Cardiovasc. Disord., 10(1), 1-9(2010). https://doi.org/10.1186/1471-2261-10-19
  40. Luo, P. and Qiu, B., "The Role of Immune Cells in Pulmonary Hypertension: Focusing on Macrophages," Hum. Immunol., 83(2), 153-163(2022).
  41. Wen, G., Zhang, C., Chen, Q., Mustafa, A., Ye, S. and Xiao, Q., "A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization," J. Biol. Chem., 290(31), 19158-19172(2015). https://doi.org/10.1074/jbc.M114.634022
  42. Liu, J., Guo, Z., Zhang, Y., Wu, T., Ma, Y., Lai, W. and Guo, Z., "LCK Inhibitor Attenuates Atherosclerosis in ApoE-/- mice via Regulating T Cell Differentiation and Reverse Cholesterol Transport," J. Mol. Cell. Cardiol., 139, 87-97(2020).
  43. Yan, A. and Gotlieb, A. I., "The Microenvironment of the Atheroma Expresses Phenotypes of Plaque Instability," Cardiovasc. Pathol., 107572(2023).
  44. Goikuria, H., Vandenbroeck, K. and Alloza, I., "Inflammation in Human Carotid Atheroma Plaques," Cytokine Growth Factor Rev., 39, 62-70(2018).
  45. Camare, C., Pucelle, M., Negre-Salvayre, A. and Salvayre, R., "Angiogenesis in the Atherosclerotic Plaque," Redox Biol., 12, 18-34(2017). https://doi.org/10.1016/j.redox.2017.01.007
  46. Perrotta, P., Veseli, B. E., Van der Veken, B., Roth, L., Martinet, W. and De Meyer, G. R., "Pharmacological Strategies to Inhibit Intra-plaque Angiogenesis in Atherosclerosis," Vasc. Pharmacol., 112, 72-78(2019). https://doi.org/10.1016/j.vph.2018.06.014
  47. Moreno, P. R., Purushothaman, M. and Purushothaman, K. R., "Plaque Neovascularization: Defense Mechanisms, Betrayal, or a War in Progress," Ann. N. Y. Acad. Sci., 1254(1), 7-17(2012).
  48. van Eif, V. W., Devalla, H. D., Boink, G. J. and Christoffels, V. M., "Transcriptional Regulation of the Cardiac Conduction System," Nat. Rev. Cardiol., 15(10), 617-630(2018). https://doi.org/10.1038/s41569-018-0031-y
  49. Lu, D. and Thum, T., "RNA-based Diagnostic and Therapeutic Strategies for Cardiovascular Disease," Nat. Rev. Cardiol., 16(11), 661-674(2019). https://doi.org/10.1038/s41569-019-0218-x
  50. Wang, Y., Chen, Y., Zhang, X., Lu, Y. and Chen, H., "New Insights in Intestinal Oxidative Stress Damage and the Health Intervention Effects of Nutrients: A Review," J. Funct. Food., 75, 104248(2020).
  51. Ighodaro, O. M. and Akinloye, O. A., "First Line Defence Antioxidants-superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX): Their Fundamental Role in the Entire Antioxidant Defence Grid," Alex. J. Med., 54(4), 287-293(2018).
  52. Jo, J., Shin, S., Jung, H., Min, B., Kim, S. and Kim, J., "Process Development for Production of Antioxidants from Lipid Extracted Microalgae Using Ultrasonic-assisted Extraction," Korean Chem. Eng. Res., 55(4), 542-547(2017).
  53. Min, B., Han, Y., Lee, D., Jo, J., Jung, H. and Kim, J. W., "Optimization of Microwave-assisted Extraction Conditions for Production of Bioactive Material from Corn Stover," Korean Chem. Eng. Res., 56(1), 66-72(2018).
  54. Pisoschi, A. M., Pop, A., Iordache, F., Stanca, L., Predoi, G. and Serban, A. I., "Oxidative Stress Mitigation by Antioxidants-an Overview on Their Chemistry and Influences on Health Status," Eur. J. Med. Chem., 209, 112891(2020).
  55. Fallah, A. A., Sarmast, E. and Jafari, T. "Effect of Dietary Anthocyanins on Biomarkers of Oxidative Stress and Antioxidative Capacity: A Systematic Review and Meta-analysis of Randomized Controlled Trials," J. Funct. Food., 68, 103912(2020).
  56. Daiber, A. and Chlopicki, S., "Revisiting Pharmacology of Oxidative Stress and Endothelial Dysfunction in Cardiovascular Disease: Evidence for Redox-based Therapies," Free Radic. Biol. Med., 157, 15-37(2020).
  57. Yalameha, B., "Antioxidant Therapy to Improve or Resolve Atherosclerosis; New Hopes and Current Trends," J. Nephropharmacology, 8(2), e18-e18(2019). https://doi.org/10.15171/npj.2019.18
  58. Yoshida, H. and Kisugi, R., "Mechanisms of LDL Oxidation," Clin. Chim. Acta, 411(23-24), 1875-1882(2010). https://doi.org/10.1016/j.cca.2010.08.038
  59. Cyr, A. R., Huckaby, L. V., Shiva, S. S. and Zuckerbraun, B. S., "Nitric Oxide and Endothelial Dysfunction," Crit. Care Clin., 36(2), 307-321(2020). https://doi.org/10.1016/j.ccc.2019.12.009
  60. Frombaum, M., Le Clanche, S., Bonnefont-Rousselot, D. and Borderie, D., "Antioxidant Effects of Resveratrol and Other Stilbene Derivatives on Oxidative Stress and NO Bioavailability: Potential Benefits to Cardiovascular Diseases," Biochimie, 94(2), 269-276 (2012).
  61. Gradinaru, D., Borsa, C., Ionescu, C. and Prada, G. I., "Oxidized LDL and NO Synthesis-biomarkers of Endothelial Dysfunction and Ageing," Mech. Ageing Dev., 151, 101-113(2015).
  62. Yang, X., Li, Y., Li, Y., Ren, X., Zhang, X., Hu, D., Gao, Y., Xing, Y. and Shang, H., "Oxidative Stress-mediated Atherosclerosis: Mechanisms and Therapies," Front. Physiol. 8, 600(2017).
  63. Schleicher, E. and Friess, U., "Oxidative Stress, AGE, and Atherosclerosis," Kidney Int., 72, S17-S26(2007). https://doi.org/10.1038/sj.ki.5002382
  64. Lee, M., Oh, S., Chu, C. H., Kim, Y. S., Na, I. C. and Park, K., "Enhancement of Membrane Durability in PEMFC by Fucoidan and Tannic Acid," Korean Chem. Eng. Res., 61(1), 45-51(2023).
  65. Zayed, A. and Ulber, R., "Fucoidan Production: Approval Key Challenges and Opportunities," Carbohydr. Polym., 211, 289-297 (2019).
  66. Pradhan, B., Patra, S., Nayak, R., Behera, C., Dash, S. R., Nayak, S., Sahu, B. B. and Jena, M., "Multifunctional Role of Fucoidan, Sulfated Polysaccharides in Human Health and Disease: A Journey Under the Sea in Pursuit of Potent Therapeutic Agents," Int. J. Biol. Macromol., 164, 4263-4278(2020).
  67. Mansour, M. B., Balti, R., Yacoubi, L., Ollivier, V., Chaubet, F. and Maaroufi, R. M., "Primary Structure and Anticoagulant Activity of Fucoidan From the Sea Cucumber Holothuria polii. Int. J. Biol. Macromol., 121, 1145-1153(2019).
  68. Pozharitskaya, O. N., Obluchinskaya, E. D. and Shikov, A. N., "Mechanisms of Bioactivities of Fucoidan From the Brown Seaweed Fucus vesiculosus L. of the Barents Sea," Mar. Drugs, 18(5), 275 (2020).
  69. Dutot, M., Grassin-Delyle, S., Salvator, H., Brollo, M., Rat, P., Fagon, R., Naline, E. and Devillier, P., "A Marine-sourced Fucoidan Solution Inhibits Toll-like-receptor-3-induced Cytokine Release by Human Bronchial Epithelial Cells," Int. J. Biol. Macromol., 130, 429-436(2019). https://doi.org/10.1016/j.ijbiomac.2019.02.113
  70. Yin, J., Wang, J., Li, F., Yang, Z., Yang, X., Sun, W., Xia, B., Li, T., Song, W. and Guo, S., "The Fucoidan From the Brown Seaweed Ascophyllum nodosum Ameliorates Atherosclerosis in Apolipoprotein E-deficient Mice," Food Funct., 10(8), 5124-5139(2019). https://doi.org/10.1039/C9FO00619B
  71. Novoyatleva, T., Kojonazarov, B., Owczarek, A., Veeroju, S., Rai, N., Henneke, I., Bohm, M., Grimminger, F., Ghofrani, H. A., Seeger, W., Weissmann, N. and Schermuly, R. T. "Evidence for the Fucoidan/P-selectin Axis as a Therapeutic Target in Hypoxia-induced Pulmonary Hypertension," Am. J. Respir. Crit. Care Med., 199(11), 1407-1420(2019). https://doi.org/10.1164/rccm.201806-1170OC
  72. Jayachandran, M., Chen, J., Chung, S. S. M. and Xu, B. "A Critical Review on the Impacts of β-glucans on Gut Microbiota and Human Health," J. Nutr. Biochem., 61, 101-110(2018).
  73. Bai, J., Ren, Y., Li, Y., Fan, M., Qian, H., Wang, L., Wu, G., Zhang, H., Qi, X., Xu, M. and Rao, Z., "Physiological Functionalities and Mechanisms of β-glucans," Trends Food Sci. Technol., 88, 57-66(2019).
  74. Gislette, T., Zhao, K. N., Gu, W. and Chen, J., "The Possible Mechanisms for β-glucans to Prevent Atherosclerotic Lesions," Curr. Bioact. Compd., 8(2), 146-150(2012). https://doi.org/10.2174/157340712801784796
  75. Wang, S., Zhou, H., Feng, T., Wu, R., Sun, X., Guan, N., Qu, L., Gao, Z., Yan, J., Nu, N. and Zhao, J., "β-glucan Attenuates Inflammatory Responses in Oxidized LDL-induced THP-1 Cells via the p38 MAPK Pathway," Nutr. Metab. Cardiovasc. Dis., 24(3), 248-255(2014). https://doi.org/10.1016/j.numecd.2013.09.019
  76. Aoki, S., Iwai, A., Kawata, K., Muramatsu, D., Uchiyama, H., Okabe, M., Ikesue, M., Maeda, N. and Uede, T., "Oral Administration of the β-glucan Produced by Aureobasidium pullulans Ameliorates Development of Atherosclerosis in Apolipoprotein E Deficient Mice," J. Funct. Foods, 18, 22-27(2015).
  77. Jiang, Y., Fu, C., Liu, G., Guo, J. and Su, Z., "Cholesterol-lowering Effects and Potential Mechanisms of Chitooligosaccharide Capsules in Hyperlipidemic Rats," Food Nutr. Res., 62(2018).
  78. Liang, S., Sun, Y. and Dai, X., "A Review of the Preparation, Analysis and Biological Functions of Chitooligosaccharide," Int. J. Mol. Sci., 19(8), 2197(2018).
  79. Yang, D., Hu, C., Deng, X., Bai, Y., Cao, H., Guo, J. and Su, Z. Therapeutic Effect of Chitooligosaccharide Tablets on Lipids in High-fat Diets Induced Hyperlipidemic Rats," Molecules, 24(3), 514(2019).
  80. Kang, N. H., Lee, W. K., Yi, B. R., Lee, H. R., Park, M. A., Park, S. K., Park, H. K. and Choi, K. C., "Risk of Cardiovascular Disease is Suppressed by Dietary Supplementation with Protamine and Chitooligosaccharide in Sprague-Dawley Rats," Mol. Med. Rep., 7(1), 127-133(2013). https://doi.org/10.3892/mmr.2012.1128
  81. Phil, L., Naveed, M., Mohammad, I. S., Bo, L. and Bin, D., "Chitooligosaccharide: An Evaluation of Physicochemical and Biological Properties with the Proposition for Determination of Thermal Degradation Products," Biomed. Pharmacother., 102, 438-451(2018).
  82. Isemura, M., "Catechin in Human Health and Disease," Molecules, 24(3), 528(2019).
  83. Miura, Y., Chiba, T., Tomita, I., Koizumi, H., Miura, S., Umegaki, K., Hara, Y. and Ikeda, M., "Tea Catechins Prevent the Development of Atherosclerosis in Apoprotein E-deficient Mice," J. Nutr., 131(1), 27-32(2001). https://doi.org/10.1093/jn/131.1.27
  84. Suzuki, J. I., Isobe, M., Morishita, R. and Nagai, R., "Tea Polyphenols Regulate Key Mediators on Inflammatory Cardiovascular Diseases," Mediat. Inflamm., 2009, 494928(2009).
  85. Malekmohammad, K., Sewell, R. D. and Rafieian-Kopaei, M., "Antioxidants and Atherosclerosis: Mechanistic Aspects," Biomolecules, 9(8), 301(2019).
  86. Risuleo, G., in Gupta, R. C.(Ed.), Resveratrol: Multiple Activities on the Biological Functionality of the Cell. Academic Press, Boston, MA, USA, 453-464(2016).
  87. Poznyak, A. V., Grechko, A. V., Orekhova, V. A., Chegodaev, Y. S., Wu, W. K. and Orekhov, A. N., "Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment," Biology, 9(3), 60(2020).
  88. Zhou, L., Long, J., Sun, Y., Chen, W., Qiu, R. and Yuan, D., "Resveratrol Ameliorates Atherosclerosis Induced by High-fat Diet and LPS in ApoE-/- Mice and Inhibits the Activation of CD4+ T Cells," Nutr. Metab., 17, 1-12(2020).
  89. Figueira, L. and Gonzalez, J. C., "Effect of Resveratrol on Seric Vascular Endothelial Growth Factor Concentrations During Atherosclerosis," Clin. Invest. Arterioscler., 30(5), 209-216(2018). https://doi.org/10.1016/j.artere.2018.08.002
  90. Bonakdar, R. A. and Guarneri, E., "Coenzyme Q10," Am. Fam. Physician, 72(6), 1065-1070(2005).
  91. Flowers, N., Hartley, L., Todkill, D., Stranges, S. and Rees, K., "Co-enzyme Q10 Supplementation for the Primary Prevention of Cardiovascular Disease," Cochrane Database Syst Rev., (12), CD010405(2014).
  92. Ulla, A., Mohamed, M. K., Sikder, B., Rahman, A. T., Sumi, F. A., Hossain, M. Reza, H. M., Rahman, G. M. S. and Alam, M. A., "Coenzyme Q10 Prevents Oxidative Stress and Fibrosis in Isoprenaline Induced Cardiac Remodeling in Aged Rats," BMC Pharmacol. Toxicol., 18(1), 1-10(2017). https://doi.org/10.1186/s40360-017-0136-7
  93. Dludla, P. V., Nyambuya, T. M., Orlando, P., Silvestri, S., Mxinwa, V., Mokgalaboni, K., Nkambule, B. B., Louw, J., Muller, C. J. F. and Tiano, L., "The Impact of Coenzyme Q10 on Metabolic and Cardiovascular Disease Profiles in Diabetic Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials," Endocrinol. Diabetes Metab., 3, e00118(2020).