THE TRIGLYCERIDES AND ATHEROGENESIS.
Keywords:
Triglycerides, atherosclerosis, triglyceride-rich lipoprotein, dyslipidemia, apo C-III.
Abstract
Triglyceride-rich lipoproteins (TRL) comprise chylomicrons, VLDL and their remnants. TRL are highly heterogeneous, differing in size, density, composition, and associated cardiovascular risk. Accumulating evidence demonstrates a strong correlationbetween the risk of cardiovascular disease (CVD) and both non-fasting (postprandial) and fasting plasma TAG level. Two mechanisms by which TRL might increase atherosclerosis are proposed: TRL remnants and VLDL are able to penetrate the arterial intima, can be internalized by macrophages and convert these cells into foam cells. Second: during lipolysis of TRL a number of inflammatory lipids are released that alter endothelial biology. TAG are not directly atherogenic but represent an important biomarker of CVD because of their association with a high concentration of small dense LDL particles, reduced HDL cholesterol levels, and with apo C-III, a proinflammatory and proatherogenic protein.
References
1. Bornfeldt, k. & Tabas, I. (2011). Insulin resistance, hyperglycemia and atherosclerosis. Cell Metab, 14(5), 575-585.
2. Millán, J., Pintó, X., Muñoz, A., Zúñiga, M., Rubiés-Prat, J., Pallardo, L., et al. (2009). Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular Prevention. Vasc Health Risk Prevent, 5, 757-765.
3. Toth, P. (2016). Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vascular Health and Risk Management, 12, 171-183.
4. Mascarenhas-Melo, F., Palabra, F., Marado, D., Sereno, J., Texeira-Lemos, E., Freitas, I., et al. (2013). Emergent biomarkers of residual cardiovascular risk in patients with low HDL-c and/or high triglycerides and average LDL-c concentrations: focus on HDL subpopulations, oxidized LDL, adiponectin, and uric acid. The Scientific World J, 2013, 1-16.
5. Cohen, D. & Fisher, E. (2013). Lipoprotein metabolism, dyslipidemia and nonalcoholic fatty liver disease. Sem Liver Dis, 33(4), 380-388.
6. Díaz, J. & Liem, A. (2005). Utilidad de la medición de la apolipoproteína B en la práctica clínica. Clin Invest Arterioscl, 7(3), 142-146.
7. Chapman, M., Ginsberg, H., Amarenco, P., Andreotti, F., Borén, J., Catapano, A., et al. (2011). Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guiadance for management. European Heart J, 32, 1345-1361.
8. Choi, S. & Ginsberg, H. (2011). Increased Very Low Density Lipoprotein secretion, hepatic steatosis, and insulin resistance. Trends Endocrinol Metab, 22(9), 353-363.
9. Klop, B., Willem, J. & Castro-Cabezas, M. (2013). Dyslipidemia in obesity: mechanisms and potential targets. Nutrients, 5, 1218-1240.
10. Welty, F. (2013). How do elevated triglycerides and low HDL-cholesterol affect inflammation and atherothrombosis? Curr Cardiol Rep, 15(9), 378-400.
11. Vergés, B. (2015). Pathophysiology of diabetic dyslipidaemia: where are we? Diabetología, 58, 886-899.
12. Daniels, T., Killinger, K., Michal, J., Wright, R. & Jiang, Z. (2009). Lipoproteins, cholesterol homeostasis and cardiac health. Int J Biol Sciences, 5(5), 474-488.
13. Nakajima, K., Nakano, T., Tokita, Y., Nagamine, T., Inazu, A., Kobayashi, J., et al. (2011). Postprandial lipoprotein metabolism; VLDL vs chylomicrons. Clin Chem Acta, 412(15-16), 1306-1318.
14. Enkhmaa, B., Ozturk, Z., Anuurad, E. & Berglund, L. (2010). Postprandial lipoproteins and cardiovascular disease risk in diabetes mellitus. Curr Diab Rep, 10, 61-69.
15. Carey, V., Bishop, L., Laranjo, N., Harshfield, B., Kwiat, C. & Sacks, F. (2010). Controbution of high plasma triglycerides and low High-Density Lipoprotein cholesterol to residual risk of coronary heart disease after establishment of Low-Density Lipoprotein cholesterol control. Am J Cardiol, 106(6), 757-763.
16. Wan, K., Zhao, J., Huang, H., Zhang, Q., Chen, X., Zeng, Z., et al. (2015). The association between Triglyceride/High Density Lipoprotein cholesterol ratio and all-cause mortality in acute coronary syndrome after coronary revascularization. PLoS ONE, 10(4), 1-11.
17. Talayero, B. & Sacks, F. (2011). The role of triglycerides in atherosclerosis. Curr Cardiol Rep, 13(6), 544-552.
18. Bitzur, R., Cohen, H., Kamari, Y., Shaish, A. & Harats, D. (2009). Triglycerides an HDL cholesterol. Diabetes Care, 32, Supplement 2, S373-S377.
19. Kannel, W. & Vasan, R. (2009). Triglycerides as vascular risk factors: new epidemiologic insights for current opinion in cardiology. Curr Opin Cardiol, 24(4), 345-350.
20. Luo, M. & Peng, D. (2016). The emerging role of apolipoprotein C-III: beyond effects on triglyceride metabolism. Lipids in Health and Disease, 15, 1-7.
21. Han, S. H., Nicholls, S., Sakuma, I., Zhao, D. & Koh, K. K. (2016). Hipertriglyceridemia and cardiovascular diseases: revisited. Korean Circulation J, 46(2), 135-144.
22. katsanos, C. (2014). Clinical considerations and mechanistic Determinants of posprandial lipemia in older adults. Adv Nutrition, 5, 226-234.
23. Dallinga-Thie, G., Kroon, J., Borén, J. & Chapman, M. (2016). Triglyceride-rich lipoproteins and remnants: targets for therapy. Curr Cardiol Rep, 18, 1-9.
24. Golberg, I., Eckel, R. & McPherson, R. (2011). Triglycerides and heart disease, still a hypothesis? Arterioscler Thromb Vasc Biol, 31(8), 1716-1725.
25. Boren, J., Matikainen, N., Adiels, M. & Taskinen, M. R. (2014). Postprandial hypertriglyceridemia as a coronary risk factor. Clin Chim Acta, 431, 31–42.
26. Rapp, J. H., Lespine, A., Hamilton, R. L., Colyvas, N., Chaumeton, A. H., Tweedie-Hardman, J., et al. (1994). Triglyceriderich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque. Arterioscler Thromb Vasc Biol, 14, 1767–1774.
27. Daugherty, A., Lange, L. G., Sobel, B. E. & Schonfeld, G (1985). Aortic accumulation and plasma clearance of b-VLDL and HDL: effects of diet-induced hypercholesterolemia in rabbits. J Lipid Res, 26, 955–963.
28. Proctor, S. D. & Mamo, J. C. L. (1998). Retention of fluorescent-labelled chylomicron remnants within the intima of the arterial wall—evidence that plaque cholesterol may be derived from post-prandial lipoproteins. Eur J Clin Invest, 28, 497–504.
29. Wang, L., Gill, R., Pedersen, T., Higgins, L., Newman, J. & Rutledge, J. C. (2009). Triglyceride-rich lipprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation. J Lipid Research, 50, 204-213.
30. den Hartigh, L., Altman, R., Norman, J. & Rutledge, J. C. (2013). Posprandial VLDL lipolysis products increase monocyte adhesion and lipid droplet formation via activation of ERK2 and NFkB. Am J Physiol Heart Circ Physiol, 306, H109-H120.
31. Qamar, A., Khetarpal, S., Khera, A., Qasim, A., Rader, D. & Reilly, M. (2015). Plasma Apo C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics. Arterioscler Thromb Vasc Biol, 35(8), 1880-1888.
32. Sacks, F. (2015). The crucial roles of Apolipoproteins E and C-III in ApoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia. Curr Opin Lipidol, 26(1), 56-63.
33. Zheng, C., Khoo, C., Furtado, J. & Sacks, F. (2010). Apolipoprotein Hypertriglyceridemia and the dense Low-Density Lipoprotein phenotype. Circulation, 121(5), 1722-1734.
34. Gordts, P., Nock, R., Son, N. H., Ramms, B., Lew, I., Gonzales, J., et al. (2016). ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors. J Clin Invest, 126(8), 2855-2866.
35. Tran-Dinh, A., Diallo, D., Delbosc, S., Varela-Pérez, M., Dang, Q. B., Lapergue, B., et al. (2013). HDL and endothelial Protection. British J Pharmacology, 169, 493-511.
36. Norata, G. & Catapano, A. (2005). Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. Vasc Health and Risk Management, 1(2), 119-129.
37. Yuhanna, I. S., Zhu, B. E., Cox, L., Hahner, S., Osborne-Lawrence, P., Lu, Y. L., et al. (2001). High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med, 7, 853-857.
38. Athyros, V., Tziomalos, K., Karangiannis, A. & Mikhailidis, D. (2011). Dyslipidaemia of obesity, metabolic syndrome and type 2 diabetes mellitus: the case for residual risk reduction after statin treatment. Open Cardiovasc Med J, 5, 24-34.
39. Shinkai, H. (2012). Cholesterol ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases. Vascular health and risk management, 8, 323-331.
40. Jung, U. J. & Choi, M. S. (2014). Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, nonalcoholic fatty liver disease. Int J Mol Sci, 15, 6184-6223.
41. Magkos, F., Mohammed, S. & Mittendorfer, B. (2008). Effect of obesity on the plasma lipoprotein subclass profile in normoglycemic and normolipidemic men and women. Int J Obes (Lond), 32(11), 1655-1664.
42. Liu, M., Chung, S., Shelness, G. & Parks, J. (2012). Hepatic ABCA1 and VLDL triglyceride production. Biochim Biophys Acta, 1821(5), 770-777.
43. Carmena, R., Duriez, P. & Fruchart, J. (2004). Atherogenic lipoprotein particles in atherosclerosis. Circulation, 15, III-2 – III-7.
44. Nikolic, D., Katsiki, N., Montalto, G., Isenovic, E., Mikhailidis, D. & Rizzo, M. (2013). Lipoprotein subfraction in metabolic syndrome and obesity: clinical significance and therapeutic approaches. Nutrients, 5, 928-948.
2. Millán, J., Pintó, X., Muñoz, A., Zúñiga, M., Rubiés-Prat, J., Pallardo, L., et al. (2009). Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular Prevention. Vasc Health Risk Prevent, 5, 757-765.
3. Toth, P. (2016). Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vascular Health and Risk Management, 12, 171-183.
4. Mascarenhas-Melo, F., Palabra, F., Marado, D., Sereno, J., Texeira-Lemos, E., Freitas, I., et al. (2013). Emergent biomarkers of residual cardiovascular risk in patients with low HDL-c and/or high triglycerides and average LDL-c concentrations: focus on HDL subpopulations, oxidized LDL, adiponectin, and uric acid. The Scientific World J, 2013, 1-16.
5. Cohen, D. & Fisher, E. (2013). Lipoprotein metabolism, dyslipidemia and nonalcoholic fatty liver disease. Sem Liver Dis, 33(4), 380-388.
6. Díaz, J. & Liem, A. (2005). Utilidad de la medición de la apolipoproteína B en la práctica clínica. Clin Invest Arterioscl, 7(3), 142-146.
7. Chapman, M., Ginsberg, H., Amarenco, P., Andreotti, F., Borén, J., Catapano, A., et al. (2011). Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guiadance for management. European Heart J, 32, 1345-1361.
8. Choi, S. & Ginsberg, H. (2011). Increased Very Low Density Lipoprotein secretion, hepatic steatosis, and insulin resistance. Trends Endocrinol Metab, 22(9), 353-363.
9. Klop, B., Willem, J. & Castro-Cabezas, M. (2013). Dyslipidemia in obesity: mechanisms and potential targets. Nutrients, 5, 1218-1240.
10. Welty, F. (2013). How do elevated triglycerides and low HDL-cholesterol affect inflammation and atherothrombosis? Curr Cardiol Rep, 15(9), 378-400.
11. Vergés, B. (2015). Pathophysiology of diabetic dyslipidaemia: where are we? Diabetología, 58, 886-899.
12. Daniels, T., Killinger, K., Michal, J., Wright, R. & Jiang, Z. (2009). Lipoproteins, cholesterol homeostasis and cardiac health. Int J Biol Sciences, 5(5), 474-488.
13. Nakajima, K., Nakano, T., Tokita, Y., Nagamine, T., Inazu, A., Kobayashi, J., et al. (2011). Postprandial lipoprotein metabolism; VLDL vs chylomicrons. Clin Chem Acta, 412(15-16), 1306-1318.
14. Enkhmaa, B., Ozturk, Z., Anuurad, E. & Berglund, L. (2010). Postprandial lipoproteins and cardiovascular disease risk in diabetes mellitus. Curr Diab Rep, 10, 61-69.
15. Carey, V., Bishop, L., Laranjo, N., Harshfield, B., Kwiat, C. & Sacks, F. (2010). Controbution of high plasma triglycerides and low High-Density Lipoprotein cholesterol to residual risk of coronary heart disease after establishment of Low-Density Lipoprotein cholesterol control. Am J Cardiol, 106(6), 757-763.
16. Wan, K., Zhao, J., Huang, H., Zhang, Q., Chen, X., Zeng, Z., et al. (2015). The association between Triglyceride/High Density Lipoprotein cholesterol ratio and all-cause mortality in acute coronary syndrome after coronary revascularization. PLoS ONE, 10(4), 1-11.
17. Talayero, B. & Sacks, F. (2011). The role of triglycerides in atherosclerosis. Curr Cardiol Rep, 13(6), 544-552.
18. Bitzur, R., Cohen, H., Kamari, Y., Shaish, A. & Harats, D. (2009). Triglycerides an HDL cholesterol. Diabetes Care, 32, Supplement 2, S373-S377.
19. Kannel, W. & Vasan, R. (2009). Triglycerides as vascular risk factors: new epidemiologic insights for current opinion in cardiology. Curr Opin Cardiol, 24(4), 345-350.
20. Luo, M. & Peng, D. (2016). The emerging role of apolipoprotein C-III: beyond effects on triglyceride metabolism. Lipids in Health and Disease, 15, 1-7.
21. Han, S. H., Nicholls, S., Sakuma, I., Zhao, D. & Koh, K. K. (2016). Hipertriglyceridemia and cardiovascular diseases: revisited. Korean Circulation J, 46(2), 135-144.
22. katsanos, C. (2014). Clinical considerations and mechanistic Determinants of posprandial lipemia in older adults. Adv Nutrition, 5, 226-234.
23. Dallinga-Thie, G., Kroon, J., Borén, J. & Chapman, M. (2016). Triglyceride-rich lipoproteins and remnants: targets for therapy. Curr Cardiol Rep, 18, 1-9.
24. Golberg, I., Eckel, R. & McPherson, R. (2011). Triglycerides and heart disease, still a hypothesis? Arterioscler Thromb Vasc Biol, 31(8), 1716-1725.
25. Boren, J., Matikainen, N., Adiels, M. & Taskinen, M. R. (2014). Postprandial hypertriglyceridemia as a coronary risk factor. Clin Chim Acta, 431, 31–42.
26. Rapp, J. H., Lespine, A., Hamilton, R. L., Colyvas, N., Chaumeton, A. H., Tweedie-Hardman, J., et al. (1994). Triglyceriderich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque. Arterioscler Thromb Vasc Biol, 14, 1767–1774.
27. Daugherty, A., Lange, L. G., Sobel, B. E. & Schonfeld, G (1985). Aortic accumulation and plasma clearance of b-VLDL and HDL: effects of diet-induced hypercholesterolemia in rabbits. J Lipid Res, 26, 955–963.
28. Proctor, S. D. & Mamo, J. C. L. (1998). Retention of fluorescent-labelled chylomicron remnants within the intima of the arterial wall—evidence that plaque cholesterol may be derived from post-prandial lipoproteins. Eur J Clin Invest, 28, 497–504.
29. Wang, L., Gill, R., Pedersen, T., Higgins, L., Newman, J. & Rutledge, J. C. (2009). Triglyceride-rich lipprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation. J Lipid Research, 50, 204-213.
30. den Hartigh, L., Altman, R., Norman, J. & Rutledge, J. C. (2013). Posprandial VLDL lipolysis products increase monocyte adhesion and lipid droplet formation via activation of ERK2 and NFkB. Am J Physiol Heart Circ Physiol, 306, H109-H120.
31. Qamar, A., Khetarpal, S., Khera, A., Qasim, A., Rader, D. & Reilly, M. (2015). Plasma Apo C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics. Arterioscler Thromb Vasc Biol, 35(8), 1880-1888.
32. Sacks, F. (2015). The crucial roles of Apolipoproteins E and C-III in ApoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia. Curr Opin Lipidol, 26(1), 56-63.
33. Zheng, C., Khoo, C., Furtado, J. & Sacks, F. (2010). Apolipoprotein Hypertriglyceridemia and the dense Low-Density Lipoprotein phenotype. Circulation, 121(5), 1722-1734.
34. Gordts, P., Nock, R., Son, N. H., Ramms, B., Lew, I., Gonzales, J., et al. (2016). ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors. J Clin Invest, 126(8), 2855-2866.
35. Tran-Dinh, A., Diallo, D., Delbosc, S., Varela-Pérez, M., Dang, Q. B., Lapergue, B., et al. (2013). HDL and endothelial Protection. British J Pharmacology, 169, 493-511.
36. Norata, G. & Catapano, A. (2005). Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. Vasc Health and Risk Management, 1(2), 119-129.
37. Yuhanna, I. S., Zhu, B. E., Cox, L., Hahner, S., Osborne-Lawrence, P., Lu, Y. L., et al. (2001). High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med, 7, 853-857.
38. Athyros, V., Tziomalos, K., Karangiannis, A. & Mikhailidis, D. (2011). Dyslipidaemia of obesity, metabolic syndrome and type 2 diabetes mellitus: the case for residual risk reduction after statin treatment. Open Cardiovasc Med J, 5, 24-34.
39. Shinkai, H. (2012). Cholesterol ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases. Vascular health and risk management, 8, 323-331.
40. Jung, U. J. & Choi, M. S. (2014). Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, nonalcoholic fatty liver disease. Int J Mol Sci, 15, 6184-6223.
41. Magkos, F., Mohammed, S. & Mittendorfer, B. (2008). Effect of obesity on the plasma lipoprotein subclass profile in normoglycemic and normolipidemic men and women. Int J Obes (Lond), 32(11), 1655-1664.
42. Liu, M., Chung, S., Shelness, G. & Parks, J. (2012). Hepatic ABCA1 and VLDL triglyceride production. Biochim Biophys Acta, 1821(5), 770-777.
43. Carmena, R., Duriez, P. & Fruchart, J. (2004). Atherogenic lipoprotein particles in atherosclerosis. Circulation, 15, III-2 – III-7.
44. Nikolic, D., Katsiki, N., Montalto, G., Isenovic, E., Mikhailidis, D. & Rizzo, M. (2013). Lipoprotein subfraction in metabolic syndrome and obesity: clinical significance and therapeutic approaches. Nutrients, 5, 928-948.
Published
2020-11-13
How to Cite
Carvajal Carvajal, C. (2020). THE TRIGLYCERIDES AND ATHEROGENESIS. Medicina Legal De Costa Rica, 34(2). Retrieved from //www.binasss.sa.cr/ojssalud/index.php/mlcr/article/view/73
Section
Literature review
The intellectual property of accepted works belongs to their authors, however access to them is totally open and free, so they can be reproduced totally or partially with the only limitation of recognizing the authorship and the source of publication (Revista Medicina Legal de Costa Rica), as long as said exploitation does not have commercial character.
