Effects of Eicosapentaenoic Acid on Arterial Calcification
Abstract
:1. Introduction
2. EPA
3. Effect of Highly Purified EPA on Cardiovascular Disease
4. Arterial Calcification in Cardiovascular Disease
4.1. Arterial Calcification and Clinical Prognosis
4.2. Arterial Calcification and Drug Therapy for Cardiovascular Disease
5. Molecular Mechanisms of Arterial Calcification
6. Inhibitory Effects of EPA on Arterial Calcification in Experimental Studies
6.1. Warfarin-Induced Arterial Calcification
6.2. Hypomorphic Klotho-Induced Arterial Calcification
6.3. Wnt Signaling-Induced Osteogenic Changes in Vascular Smooth Muscle Cells
6.4. Palmitic Acid-Induced Osteogenic Changes in Vascular Smooth Muscle Cells
6.5. Statin-Induced Interleukin 1β (IL-1β)-Mediated Arterial Calcification
7. Effects of EPA on Arterial Calcification in Clinical Studies
8. Future Challenges and Possible Solutions
8.1. Activation of GPR120 Signaling
8.2. Activation of ChemR23 Signaling
8.3. Identification of Other Specific Targets of EPA
9. Summary
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
EPA | eicosapentaenoic acid |
CKD | chronic kidney disease |
LDL-C | low-density lipoprotein-cholesterol |
RCT | randomized controlled trial |
CT | computed tomography |
PCSK9 | proprotein convertase subtilisin-kexin type 9 |
MGP | matrix Gla protein |
BMP | bone morphogenetic protein |
MMP | matrix metalloproteinase |
MCP-1 | Monocyte chemotactic protein-1 |
NOX4 | NADPH oxidase-4 |
GPR120 | G-protein coupled receptor 120 |
PPARγ | peroxisome proliferator-activating receptor gamma |
SFRP2 | Secreted frizzled-related protein 2 |
SCD | Stearoyl-CoA desaturase |
ACSL3 | Acyl-CoA synthetase long chain family member 3 |
NF-κB | Nuclear factor-κB |
IL-1β | interleukin 1β |
DHA | Docosahexaenoic acid |
References
- Madhavan, M.V.; Tarigopula, M.; Mintz, G.S.; Maehara, A.; Stone, G.W.; Genereux, P. Coronary artery calcification: Pathogenesis and prognostic implications. J. Am. Coll. Cardiol. 2014, 63, 1703–1714. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Budoff, M.J.; Shaw, L.J.; Liu, S.T.; Weinstein, S.R.; Tseng, P.H.; Flores, F.R.; Callister, T.Q.; Raggi, P.; Berman, D.S.; Mosler, T.P. Long-Term Prognosis Associated With Coronary Calcification: Observations From a Registry of 25,253 Patients. J. Am. Coll. Cardiol. 2007, 49, 1860–1870. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Verbeke, F.; van Biesen, W.; Honkanen, E.; Wikström, B.; Jensen, P.B.; Krzesinski, J.-M.; Rasmussen, M.; Vanholder, R.; Rensma, P.L. Prognostic Value of Aortic Stiffness and Calcification for Cardiovascular Events and Mortality in Dialysis Patients: Outcome of the Calcification Outcome in Renal Disease (CORD) Study. Clin. J. Am. Soc. Nephrol. 2011, 6, 153. [Google Scholar] [CrossRef]
- Akers, E.J.; Nicholls, S.J.; Bartolo, B.A.D. Plaque Calcification. Arterioscler. Thromb. Vasc. Biol. 2019, 39, 1902–1910. [Google Scholar] [CrossRef]
- Shi, X.; Gao, J.; Lv, Q.; Cai, H.; Wang, F.; Ye, R.; Liu, X. Calcification in Atherosclerotic Plaque Vulnerability: Friend or Foe? Front. Physiol. 2020, 11, 56. [Google Scholar] [CrossRef]
- Mackey, R.H.; Venkitachalam, L.; Sutton-Tyrrell, K. Calcifications, arterial stiffness and atherosclerosis. Adv. Cardiol. 2007, 44, 234–244. [Google Scholar]
- Mattace-Raso, F.U.S.; van der Cammen, T.J.M.; Hofman, A.; van Popele, N.M.; Bos, M.L.; Schalekamp, M.A.D.H.; Asmar, R.; Reneman, R.S.; Hoeks, A.P.G.; Breteler, M.M.B.; et al. Arterial Stiffness and Risk of Coronary Heart Disease and Stroke. Circulation 2006, 113, 657–663. [Google Scholar] [CrossRef] [Green Version]
- Henein, M.; Granåsen, G.; Wiklund, U.; Schmermund, A.; Guerci, A.; Erbel, R.; Raggi, P. High dose and long-term statin therapy accelerate coronary artery calcification. Int. J. Cardiol. 2015, 184, 581–586. [Google Scholar] [CrossRef] [PubMed]
- Baigent, C.; Keech, A.; Kearney, P.M.; Blackwell, L.; Buck, G.; Pollicino, C.; Kirby, A.; Sourjina, T.; Peto, R.; Collins, R.; et al. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005, 366, 1267–1278. [Google Scholar]
- Saremi, A.; Bahn, G.; Reaven, P.D. Progression of vascular calcification is increased with statin use in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care 2012, 35, 2390–2392. [Google Scholar] [CrossRef] [Green Version]
- Budoff, M.; Brent Muhlestein, J.; Le, V.T.; May, H.T.; Roy, S.; Nelson, J.R. Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200–499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study. Clin. Cardiol. 2018, 41, 13–19. [Google Scholar] [CrossRef]
- Shea, M.K.; O’Donnell, C.J.; Hoffmann, U.; Dallal, G.E.; Dawson-Hughes, B.; Ordovas, J.M.; Price, P.A.; Williamson, M.K.; Booth, S.L. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am. J. Clin. Nutr. 2009, 89, 1799–1807. [Google Scholar] [CrossRef] [PubMed]
- Krueger, T.; Schlieper, G.; Schurgers, L.; Cornelis, T.; Cozzolino, M.; Jacobi, J.; Jadoul, M.; Ketteler, M.; Rump, L.C.; Stenvinkel, P.; et al. Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): A rationale and study protocol. Nephrol. Dial. Transpl. 2014, 29, 1633–1638. [Google Scholar] [CrossRef] [PubMed]
- Ikegami, Y.; Inoue, I.; Inoue, K.; Shinoda, Y.; Iida, S.; Goto, S.; Nakano, T.; Shimada, A.; Noda, M. The annual rate of coronary artery calcification with combination therapy with a PCSK9 inhibitor and a statin is lower than that with statin monotherapy. NPJ. Aging. Mech. Dis. 2018, 4, 7. [Google Scholar] [CrossRef] [PubMed]
- Ter Braake, A.D.; Smit, A.E.; Bos, C.; van Herwaarden, A.E.; Alkema, W.; van Essen, H.W.; Bravenboer, N.; Vervloet, M.G.; Hoenderop, J.G.J.; de Baaij, J.H.F. Magnesium prevents vascular calcification in Klotho deficiency. Kidney Int. 2020, 97, 487–501. [Google Scholar] [CrossRef]
- Voelkl, J.; Alesutan, I.; Leibrock, C.B.; Quintanilla-Martinez, L.; Kuhn, V.; Feger, M.; Mia, S.; Ahmed, M.S.E.; Rosenblatt, K.P.; Kuro-O, M.; et al. Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice. J. Clin Investig. 2013, 123, 812–822. [Google Scholar] [PubMed] [Green Version]
- Abedin, M.; Lim, J.; Tang, T.B.; Park, D.; Demer, L.L.; Tintut, Y. N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-gamma pathways. Circ. Res. 2006, 98, 727–729. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, K.; Miura, D.; Saito, Y.; Yunoki, K.; Koyama, Y.; Satoh, M.; Kondo, M.; Osawa, K.; Hatipoglu, O.F.; Miyoshi, T.; et al. Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice. PLoS ONE 2017, 12, e0181009. [Google Scholar] [CrossRef] [Green Version]
- Kanai, S.; Uto, K.; Honda, K.; Hagiwara, N.; Oda, H. Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats. Atherosclerosis 2011, 215, 43–51. [Google Scholar] [CrossRef]
- Wei, M.Y.; Jacobson, T.A. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: A systematic review and meta-analysis. Curr. Atheroscler. Rep. 2011, 13, 474–483. [Google Scholar] [CrossRef]
- Jacobson, T.A.; Glickstein, S.B.; Rowe, J.D.; Soni, P.N. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: A review. J. Clin. Lipidol. 2012, 6, 5–18. [Google Scholar] [CrossRef] [PubMed]
- Bhatt, D.L.; Steg, P.G.; Miller, M.; Brinton, E.A.; Jacobson, T.A.; Ketchum, S.B.; Doyle, R.T., Jr.; Juliano, R.A.; Jiao, L.; Granowitz, C.; et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N. Engl. J. Med. 2019, 380, 11–22. [Google Scholar] [CrossRef]
- Yokoyama, M.; Origasa, H.; Matsuzaki, M.; Matsuzawa, Y.; Saito, Y.; Ishikawa, Y.; Oikawa, S.; Sasaki, J.; Hishida, H.; Itakura, H.; et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis. Lancet 2007, 369, 1090–1098. [Google Scholar] [CrossRef]
- Bhatt, D.L.; Miller, M.; Brinton, E.A.; Jacobson, T.A.; Steg, P.G.; Ketchum, S.B.; Doyle, R.T., Jr.; Juliano, R.A.; Jiao, L.; Granowitz, C.; et al. REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States. Circulation 2020, 141, 367–375. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bittner, D.O.; Goeller, M.; Zopf, Y.; Achenbach, S.; Marwan, M. Early-onset coronary atherosclerosis in patients with low levels of omega-3 fatty acids. Eur. J. Clin. Nutr. 2020, 74, 651–656. [Google Scholar] [CrossRef] [PubMed]
- Miyoshi, T.; Kohno, K.; Asonuma, H.; Sakuragi, S.; Nakahama, M.; Kawai, Y.; Uesugi, T.; Oka, T.; Munemasa, M.; Takahashi, N.; et al. Effect of Intensive and Standard Pitavastatin Treatment With or Without Eicosapentaenoic Acid on Progression of Coronary Artery Calcification Over 12 Months- Prospective Multicenter Study. Circ. J. 2018, 82, 532–540. [Google Scholar] [CrossRef] [Green Version]
- Sekikawa, A.; Mahajan, H.; Kadowaki, S.; Hisamatsu, T.; Miyagawa, N.; Fujiyoshi, A.; Kadota, A.; Maegawa, H.; Murata, K.; Miura, K.; et al. Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men. Eur. J. Clin. Nutr. 2019, 73, 783–792. [Google Scholar] [CrossRef]
- Sekikawa, A.; Miura, K.; Lee, S.; Fujiyoshi, A.; Edmundowicz, D.; Kadowaki, T.; Evans, R.W.; Kadowaki, S.; Sutton-Tyrrell, K.; Okamura, T.; et al. Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese men in Japan and white men in the USA: Population based prospective cohort study. Heart 2014, 100, 569–573. [Google Scholar] [CrossRef] [Green Version]
- Serhan, C.N.; Hong, S.; Gronert, K.; Colgan, S.P.; Devchand, P.R.; Mirick, G.; Moussignac, R.L. Resolvins: A family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 2002, 196, 1025–1037. [Google Scholar] [CrossRef] [Green Version]
- Schwab, J.M.; Chiang, N.; Arita, M.; Serhan, C.N. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007, 447, 869–874. [Google Scholar] [CrossRef] [Green Version]
- Boekholdt, S.M.; Hovingh, G.K.; Mora, S.; Arsenault, B.J.; Amarenco, P.; Pedersen, T.R.; LaRosa, J.C.; Waters, D.D.; DeMicco, D.A.; Simes, R.J.; et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: A meta-analysis of statin trials. J. Am. Coll. Cardiol. 2014, 64, 485–494. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ginsberg, H.N.; Elam, M.B.; Lovato, L.C.; Crouse 3rd, J.R.; Leiter, L.A.; Linz, P.; Friedewald, W.T.; Buse, J.B.; Gerstein, H.C.; Probstfield, J.; et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med. 2010, 362, 1563–1574. [Google Scholar] [PubMed]
- Group, H.T.C.; Landray, M.J.; Haynes, R.; Hopewell, J.C.; Parish, S.; Aung, T.; Tomson, J.; Wallendszus, K.; Craig, M.; Jiang, L.; et al. Effects of extended-release niacin with laropiprant in high-risk patients. N. Engl. J. Med. 2014, 371, 203–212. [Google Scholar]
- Investigators, A.-H. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am. Heart J. 2011, 161, 471–477. [Google Scholar]
- Investigators, O.T.; Bosch, J.; Gerstein, H.C.; Dagenais, G.R.; Diaz, R.; Dyal, L.; Jung, H.; Maggiono, A.P.; Probstfield, J.; Ramachandran, A.; et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N. Engl. J. Med. 2012, 367, 309–318. [Google Scholar] [CrossRef] [Green Version]
- Group, A.S.C.; Bowman, L.; Mafham, M.; Wallendszus, K.; Stevens, W.; Buck, G.; Barton, J.; Murphy, K.; Aung, T.; Haynes, R.; et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N. Engl. J. Med. 2018, 379, 1540–1550. [Google Scholar]
- Aung, T.; Halsey, J.; Kromhout, D.; Gerstein, H.C.; Marchioli, R.; Tavazzi, L.; Geleijnse, J.M.; Rauch, B.; Ness, A.; Galan, P.; et al. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77917 Individuals. JAMA. Cardiol. 2018, 3, 225–234. [Google Scholar] [CrossRef] [Green Version]
- Borow, K.M.; Nelson, J.R.; Mason, R.P. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis 2015, 242, 357–366. [Google Scholar] [CrossRef] [Green Version]
- Tani, S.; Nagao, K.; Matsumoto, M.; Hirayama, A. Highly Purified Eicosapentaenoic Acid May Increase Low-Density Lipoprotein Particle Size by Improving Triglyceride Metabolism in Patients With Hypertriglyceridemia. Circ. J. 2013, 77, 2349–2357. [Google Scholar] [CrossRef] [Green Version]
- Satoh, N.; Shimatsu, A.; Kotani, K.; Sakane, N.; Yamada, K.; Suganami, T.; Kuzuya, H.; Ogawa, Y. Purified Eicosapentaenoic Acid Reduces Small Dense LDL, Remnant Lipoprotein Particles, and C-Reactive Protein in Metabolic Syndrome. Diabetes Care 2007, 30, 144. [Google Scholar] [CrossRef] [Green Version]
- Nakajima, K.; Yamashita, T.; Kita, T.; Takeda, M.; Sasaki, N.; Kasahara, K.; Shinohara, M.; Rikitake, Y.; Ishida, T.; Yokoyama, M.; et al. Orally Administered Eicosapentaenoic Acid Induces Rapid Regression of Atherosclerosis Via Modulating the Phenotype of Dendritic Cells in LDL Receptor-Deficient Mice. Arter. Thromb. Vasc. Biol. 2011, 31, 1963–1972. [Google Scholar] [CrossRef] [Green Version]
- Matsumoto, M.; Sata, M.; Fukuda, D.; Tanaka, K.; Soma, M.; Hirata, Y.; Nagai, R. Orally administered eicosapentaenoic acid reduces and stabilizes atherosclerotic lesions in ApoE-deficient mice. Atherosclerosis 2008, 197, 524–533. [Google Scholar] [CrossRef]
- Kamata, R.; Bumdelger, B.; Kokubo, H.; Fujii, M.; Yoshimura, K.; Ishida, T.; Ishida, M.; Yoshizumi, M. EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4. PLoS ONE 2016, 11, e0165132. [Google Scholar] [CrossRef]
- Sato, T.; Horikawa, M.; Takei, S.; Yamazaki, F.; Ito, T.K.; Kondo, T.; Sakurai, T.; Kahyo, T.; Ikegami, K.; Sato, S.; et al. Preferential Incorporation of Administered Eicosapentaenoic Acid Into Thin-Cap Atherosclerotic Plaques. Arterioscler. Thromb. Vasc. Biol. 2019, 39, 1802–1816. [Google Scholar] [CrossRef]
- Kronmal, R.A.; McClelland, R.L.; Detrano, R.; Shea, S.; Lima, J.A.; Cushman, M.; Bild, D.E.; Burke, G.L. Risk factors for the progression of coronary artery calcification in asymptomatic subjects: Results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2007, 115, 2722–2730. [Google Scholar] [CrossRef] [Green Version]
- Budoff, M.J.; Hokanson, J.E.; Nasir, K.; Shaw, L.J.; Kinney, G.L.; Chow, D.; Demoss, D.; Nuguri, V.; Nabavi, V.; Ratakonda, R.; et al. Progression of coronary artery calcium predicts all-cause mortality. JACC Cardiovasc. Imaging 2010, 3, 1229–1236. [Google Scholar] [CrossRef] [Green Version]
- Amann, K. Media Calcification and Intima Calcification Are Distinct Entities in Chronic Kidney Disease. Clin. J. Am. Soc. Nephrol. 2008, 3, 1599. [Google Scholar] [CrossRef] [Green Version]
- Zazzeroni, L.; Faggioli, G.; Pasquinelli, G. Mechanisms of Arterial Calcification: The Role of Matrix Vesicles. Eur. J. Vasc. Endovasc. Surg. 2018, 55, 425–432. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Osborne, M.T.; Tung, B.; Li, M.; Li, Y. Imaging Cardiovascular Calcification. J. Am. Heart Assoc. 2018, 7, e008564. [Google Scholar]
- Blacher, J.; Guerin Alain, P.; Pannier, B.; Marchais Sylvain, J.; London Gérard, M. Arterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease. Hypertension 2001, 38, 938–942. [Google Scholar] [CrossRef] [Green Version]
- Rennenberg, R.J.; Kessels, A.G.; Schurgers, L.J.; van Engelshoven, J.M.; de Leeuw, P.W.; Kroon, A.A. Vascular calcifications as a marker of increased cardiovascular risk: A meta-analysis. Vasc. Health. Risk. Manag. 2009, 5, 185–197. [Google Scholar] [CrossRef] [Green Version]
- Vengrenyuk, Y.; Carlier, S.; Xanthos, S.; Cardoso, L.; Ganatos, P.; Virmani, R.; Einav, S.; Gilchrist, L.; Weinbaum, S. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc. Natl. Acad. Sci. USA 2006, 103, 14678–14683. [Google Scholar] [CrossRef] [Green Version]
- Kelly-Arnold, A.; Maldonado, N.; Laudier, D.; Aikawa, E.; Cardoso, L.; Weinbaum, S. Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc. Natl. Acad. Sci. USA 2013, 110, 10741–10746. [Google Scholar] [CrossRef] [Green Version]
- Huang, H.; Virmani, R.; Younis, H.; Burke, A.P.; Kamm, R.D.; Lee, R.T. The Impact of Calcification on the Biomechanical Stability of Atherosclerotic Plaques. Circulation 2001, 103, 1051–1056. [Google Scholar] [CrossRef] [Green Version]
- Vengrenyuk, Y.; Cardoso, L.; Weinbaum, S. Micro-CT based analysis of a new paradigm for vulnerable plaque rupture: Cellular microcalcifications in fibrous caps. Mol. Cell Biomech. 2008, 5, 37–47. [Google Scholar]
- Guérin, A.P.; London, G.M.; Marchais, S.J.; Metivier, F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol. Dial. Transplant. 2000, 15, 1014–1021. [Google Scholar] [CrossRef] [Green Version]
- Osawa, K.; Miyoshi, T.; Oe, H.; Sato, S.; Nakamura, K.; Kohno, K.; Morita, H.; Kanazawa, S.; Ito, H. Association between coronary artery calcification and left ventricular diastolic dysfunction in elderly people. Heart Vessel. 2016, 31, 499–507. [Google Scholar] [CrossRef]
- Nakazato, R.; Gransar, H.; Berman, D.S.; Cheng, V.Y.; Lin, F.Y.; Achenbach, S.; Al-Mallah, M.; Budoff, M.J.; Cademartiri, F.; Callister, T.Q.; et al. Statins use and coronary artery plaque composition: Results from the International Multicenter CONFIRM Registry. Atherosclerosis 2012, 225, 148–153. [Google Scholar] [CrossRef] [Green Version]
- Puri, R.; Nicholls, S.J.; Shao, M.; Kataoka, Y.; Uno, K.; Kapadia, S.R.; Tuzcu, E.M.; Nissen, S.E. Impact of Statins on Serial Coronary Calcification During Atheroma Progression and Regression. J. Am. Coll. Cardiol. 2015, 65, 1273–1282. [Google Scholar] [CrossRef]
- Healy, A.; Berus, J.M.; Christensen, J.L.; Lee, C.; Mantsounga, C.; Dong, W.; Watts, J.P.; Assali, M.; Ceneri, N.; Nilson, R.; et al. Statins Disrupt Macrophage Rac1 Regulation Leading to Increased Atherosclerotic Plaque Calcification. Arterioscler. Thromb. Vasc. Biol. 2020, 40, 714–732. [Google Scholar] [CrossRef]
- Ceneri, N.; Zhao, L.; Young, B.D.; Healy, A.; Coskun, S.; Vasavada, H.; Yarovinsky, T.O.; Ike, K.; Pardi, R.; Qin, L.; et al. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production. Arterioscler. Thromb. Vasc. Biol. 2017, 37, 328–340. [Google Scholar] [CrossRef] [Green Version]
- Fu, H.; Alabdullah, M.; Großmann, J.; Spieler, F.; Abdosh, R.; Lutz, V.; Kalies, K.; Knöpp, K.; Rieckmann, M.; Koch, S.; et al. The differential statin effect on cytokine production of monocytes or macrophages is mediated by differential geranylgeranylation-dependent Rac1 activation. Cell Death Dis. 2019, 10, 880. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.; Zhang, H.W.; Li, S.; Zhang, Y.; Xu, R.X.; Zhu, C.G.; Wu, N.Q.; Guo, Y.L.; Qing, P.; Li, X.L.; et al. Association between plasma proprotein convertase subtisilin/kexin type 9 concentration and coronary artery calcification. Ann. Clin. Biochem. 2018, 55, 158–164. [Google Scholar] [CrossRef] [Green Version]
- Nozue, T. Lipid Lowering Therapy and Circulating PCSK9 Concentration. J. Atheroscler Thromb. 2017, 24, 895–907. [Google Scholar] [CrossRef] [Green Version]
- Nicholls, S.J.; Puri, R.; Anderson, T.; Ballantyne, C.M.; Cho, L.; Kastelein, J.J.P.; Koenig, W.; Somaratne, R.; Kassahun, H.; Yang, J.; et al. Effect of Evolocumab on Coronary Plaque Composition. J. Am. Coll Cardiol. 2018, 72, 2012–2021. [Google Scholar] [CrossRef]
- Shao, J.S.; Cai, J.; Towler, D.A. Molecular mechanisms of vascular calcification: Lessons learned from the aorta. Arter. Thromb. Vasc. Biol. 2006, 26, 1423–1430. [Google Scholar] [CrossRef]
- Nakahara, T.; Dweck, M.R.; Narula, N.; Pisapia, D.; Narula, J.; Strauss, H.W. Coronary Artery Calcification: From Mechanism to Molecular Imaging. Jacc. Cardiovasc. Imaging 2017, 10, 582–593. [Google Scholar] [CrossRef]
- Abdelbaky, A.; Corsini, E.; Figueroa Amparo, L.; Fontanez, S.; Subramanian, S.; Ferencik, M.; Brady Thomas, J.; Hoffmann, U.; Tawakol, A. Focal Arterial Inflammation Precedes Subsequent Calcification in the Same Location. Circ. Cardiovasc. Imaging 2013, 6, 747–754. [Google Scholar] [CrossRef] [Green Version]
- Cozzolino, M.; Brancaccio, D.; Gallieni, M.; Slatopolsky, E. Pathogenesis of vascular calcification in chronic kidney disease. Kidney Int. 2005, 68, 429–436. [Google Scholar] [CrossRef] [Green Version]
- Van Campenhout, A.; Golledge, J. Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis 2009, 204, 321–329. [Google Scholar] [CrossRef] [Green Version]
- Giachelli, C.M.; Speer, M.Y.; Li, X.; Rajachar, R.M.; Yang, H. Regulation of vascular calcification: Roles of phosphate and osteopontin. Circ. Res. 2005, 96, 717–722. [Google Scholar] [CrossRef] [Green Version]
- Vassalle, C.; Iervasi, G. New insights for matrix Gla protein, vascular calcification and cardiovascular risk and outcome. Atherosclerosis 2014, 235, 236–238. [Google Scholar] [CrossRef] [PubMed]
- Lomashvili, K.A.; Narisawa, S.; Millán, J.L.; O’Neill, W.C. Vascular calcification is dependent on plasma levels of pyrophosphate. Kidney Int. 2014, 85, 1351–1356. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schurgers, L.J.; Akbulut, A.C.; Kaczor, D.M.; Halder, M.; Koenen, R.R.; Kramann, R. Initiation and Propagation of Vascular Calcification is Regulated by a Concert of Platelet- and Smooth Muscle Cell-Derived Extracellular Vesicles. Front. Cardiovasc. Med. 2018, 5, 36. [Google Scholar] [CrossRef]
- Proudfoot, D.; Skepper, J.N.; Hegyi, L.; Bennett, M.R.; Shanahan, C.M.; Weissberg, P.L. Apoptosis regulates human vascular calcification in vitro: Evidence for initiation of vascular calcification by apoptotic bodies. Circ. Res. 2000, 87, 1055–1062. [Google Scholar] [CrossRef] [Green Version]
- Thompson, B.; Towler, D.A. Arterial calcification and bone physiology: Role of the bone-vascular axis. Nat. Rev. Endocrinol. 2012, 8, 529–543. [Google Scholar] [CrossRef] [Green Version]
- Lee, S.J.; Lee, I.K.; Jeon, J.H. Vascular Calcification-New Insights Into Its Mechanism. Int. J. Mol. Sci. 2020, 21, 2685. [Google Scholar] [CrossRef] [Green Version]
- Saito, Y.; Nakamura, K.; Miura, D.; Yunoki, K.; Miyoshi, T.; Yoshida, M.; Kawakita, N.; Kimura, T.; Kondo, M.; Sarashina, T.; et al. Suppression of Wnt Signaling and Osteogenic Changes in Vascular Smooth Muscle Cells by Eicosapentaenoic Acid. Nutrients 2017, 9, 858. [Google Scholar] [CrossRef] [Green Version]
- Kageyama, A.; Matsui, H.; Ohta, M.; Sambuichi, K.; Kawano, H.; Notsu, T.; Imada, K.; Yokoyama, T.; Kurabayashi, M. Palmitic Acid Induces Osteoblastic Differentiation in Vascular Smooth Muscle Cells through ACSL3 and NF-κB, Novel Targets of Eicosapentaenoic Acid. PLoS ONE 2013, 8, e68197. [Google Scholar] [CrossRef] [Green Version]
- Luo, G.; Ducy, P.; McKee, M.D.; Pinero, G.J.; Loyer, E.; Behringer, R.R.; Karsenty, G. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997, 386, 78–81. [Google Scholar] [CrossRef]
- Speer, M.Y.; McKee, M.D.; Guldberg, R.E.; Liaw, L.; Yang, H.Y.; Tung, E.; Karsenty, G.; Giachelli, C.M. Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: Evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J. Exp. Med. 2002, 196, 1047–1055. [Google Scholar] [CrossRef] [PubMed]
- Jaminon, A.M.G.; Dai, L.; Qureshi, A.R.; Evenepoel, P.; Ripsweden, J.; Söderberg, M.; Witasp, A.; Olauson, H.; Schurgers, L.J.; Stenvinkel, P. Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease. Sci. Rep. 2020, 10, 6586. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zebboudj, A.F.; Imura, M.; Boström, K. Matrix GLA Protein, a Regulatory Protein for Bone Morphogenetic Protein-2. J. Biol. Chem. 2002, 277, 4388–4394. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zebboudj, A.F.; Shin, V.; Boström, K. Matrix GLA protein and BMP-2 regulate osteoinduction in calcifying vascular cells. J. Cell. Biochem. 2003, 90, 756–765. [Google Scholar] [CrossRef]
- Schurgers, L.J.; Teunissen, K.J.; Knapen, M.H.; Kwaijtaal, M.; van Diest, R.; Appels, A.; Reutelingsperger, C.P.; Cleutjens, J.P.; Vermeer, C. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: Undercarboxylated matrix Gla protein as marker for vascular calcification. Arter. Thromb. Vasc. Biol. 2005, 25, 1629–1633. [Google Scholar] [CrossRef] [Green Version]
- Demer, L.L.; Boström, K.I. Conflicting forces of warfarin and matrix gla protein in the artery wall. Arter. Thromb. Vasc. Biol. 2015, 35, 9–10. [Google Scholar] [CrossRef] [Green Version]
- Price, P.A.; Faus, S.A.; Williamson, M.K. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arter. Thromb. Vasc. Biol. 1998, 18, 1400–1407. [Google Scholar] [CrossRef] [Green Version]
- Price, P.A.; Kaneda, Y. Vitamin K counteracts the effect of warfarin in liver but not in bone. Thromb. Res. 1987, 46, 121–131. [Google Scholar] [CrossRef]
- Kuro-o, M.; Matsumura, Y.; Aizawa, H.; Kawaguchi, H.; Suga, T.; Utsugi, T.; Ohyama, Y.; Kurabayashi, M.; Kaname, T.; Kume, E.; et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997, 390, 45–51. [Google Scholar] [CrossRef]
- Kurosu, H.; Yamamoto, M.; Clark, J.D.; Pastor, J.V.; Nandi, A.; Gurnani, P.; McGuinness, O.P.; Chikuda, H.; Yamaguchi, M.; Kawaguchi, H.; et al. Suppression of aging in mice by the hormone Klotho. Science 2005, 309, 1829–1833. [Google Scholar] [CrossRef] [Green Version]
- Semba, R.D.; Cappola, A.R.; Sun, K.; Bandinelli, S.; Dalal, M.; Crasto, C.; Guralnik, J.M.; Ferrucci, L. Plasma klotho and mortality risk in older community-dwelling adults. J. Gerontol. A Biol. Sci. Med. Sci 2011, 66, 794–800. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Semba, R.D.; Cappola, A.R.; Sun, K.; Bandinelli, S.; Dalal, M.; Crasto, C.; Guralnik, J.M.; Ferrucci, L. Plasma klotho and cardiovascular disease in adults. J. Am. Geriatr. Soc. 2011, 59, 1596–1601. [Google Scholar] [CrossRef] [Green Version]
- Kitagawa, M.; Sugiyama, H.; Morinaga, H.; Inoue, T.; Takiue, K.; Ogawa, A.; Yamanari, T.; Kikumoto, Y.; Uchida, H.A.; Kitamura, S.; et al. A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS ONE 2013, 8, e56695. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koh, N.; Fujimori, T.; Nishiguchi, S.; Tamori, A.; Shiomi, S.; Nakatani, T.; Sugimura, K.; Kishimoto, T.; Kinoshita, S.; Kuroki, T.; et al. Severely Reduced Production of Klotho in Human Chronic Renal Failure Kidney. Biochem. Biophys. Res. Commun. 2001, 280, 1015–1020. [Google Scholar] [CrossRef] [PubMed]
- Griendling, K.K.; Sorescu, D.; Ushio-Fukai, M. NAD(P)H Oxidase. Circ. Res. 2000, 86, 494–501. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Byon, C.H.; Javed, A.; Dai, Q.; Kappes, J.C.; Clemens, T.L.; Darley-Usmar, V.M.; McDonald, J.M.; Chen, Y. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J. Biol. Chem. 2008, 283, 15319–15327. [Google Scholar] [CrossRef] [Green Version]
- Hu, M.C.; Shi, M.; Zhang, J.; Quiñones, H.; Griffith, C.; Kuro-o, M.; Moe, O.W. Klotho deficiency causes vascular calcification in chronic kidney disease. J. Am. Soc. Nephrol. 2011, 22, 124–136. [Google Scholar] [CrossRef]
- Nusse, R.; Clevers, H. Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell 2017, 169, 985–999. [Google Scholar] [CrossRef]
- Steinhart, Z.; Angers, S. Wnt signaling in development and tissue homeostasis. Development 2018, 145, dev146589. [Google Scholar] [CrossRef] [Green Version]
- Lehmann, M.; Baarsma, H.A.; Königshoff, M. WNT Signaling in Lung Aging and Disease. Ann. Am. Thorac. Soc. 2016, 13, s411–s416. [Google Scholar] [CrossRef]
- Yang, H.C.; Fogo, A.B. Fibrosis and renal aging. Kidney Int. Suppl. 2014, 4, 75–78. [Google Scholar] [CrossRef] [Green Version]
- Freise, C.; Kretzschmar, N.; Querfeld, U. Wnt signaling contributes to vascular calcification by induction of matrix metalloproteinases. BMC Cardiovasc. Disord. 2016, 16, 185. [Google Scholar] [CrossRef] [Green Version]
- Albanese, I.; Khan, K.; Barratt, B.; Al-Kindi, H.; Schwertani, A. Atherosclerotic Calcification: Wnt Is the Hint. J. Am. Heart Assoc. 2018, 7, 4. [Google Scholar] [CrossRef] [Green Version]
- Shao, J.S.; Cheng, S.L.; Pingsterhaus, J.M.; Charlton-Kachigian, N.; Loewy, A.P.; Towler, D.A. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J. Clin. Investig. 2005, 115, 1210–1220. [Google Scholar] [CrossRef] [Green Version]
- Liu, H.; Fergusson, M.M.; Castilho, R.M.; Liu, J.; Cao, L.; Chen, J.; Malide, D.; Rovira, I.I.; Schimel, D.; Kuo, C.J.; et al. Augmented Wnt signaling in a mammalian model of accelerated aging. Science 2007, 317, 803–806. [Google Scholar] [CrossRef] [Green Version]
- Song, K.S.; Jing, K.; Kim, J.S.; Yun, E.J.; Shin, S.; Seo, K.S.; Park, J.H.; Heo, J.Y.; Kang, J.X.; Suh, K.S.; et al. Omega-3-polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt/Beta-catenin signaling. Pancreatology 2011, 11, 574–584. [Google Scholar] [CrossRef]
- Devi, K.P.; Rajavel, T.; Russo, G.L.; Daglia, M.; Nabavi, S.F.; Nabavi, S.M. Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy. Anticancer Agents Med. Chem. 2015, 15, 888–895. [Google Scholar] [CrossRef]
- Cai, T.; Sun, D.; Duan, Y.; Wen, P.; Dai, C.; Yang, J.; He, W. WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression. Exp. Cell Res. 2016, 345, 206–217. [Google Scholar] [CrossRef] [Green Version]
- Woldt, E.; Terrand, J.; Mlih, M.; Matz, R.L.; Bruban, V.; Coudane, F.; Foppolo, S.; El Asmar, Z.; Chollet, M.E.; Ninio, E.; et al. The nuclear hormone receptor PPARγ counteracts vascular calcification by inhibiting Wnt5a signalling in vascular smooth muscle cells. Nat. Commun. 2012, 3, 1077. [Google Scholar] [CrossRef] [Green Version]
- Boucher, P.; Matz, R.L.; Terrand, J. atherosclerosis: Gone with the Wnt? Atherosclerosis 2020, 301, 15–22. [Google Scholar] [CrossRef]
- Cohen, P.; Miyazaki, M.; Socci, N.D.; Hagge-Greenberg, A.; Liedtke, W.; Soukas, A.A.; Sharma, R.; Hudgins, L.C.; Ntambi, J.M.; Friedman, J.M. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science 2002, 297, 240–243. [Google Scholar] [CrossRef] [PubMed]
- Paton, C.M.; Ntambi, J.M. Biochemical and physiological function of stearoyl-CoA desaturase. Am. J. Physiol. Endocrinol. Metab. 2009, 297, E28–E37. [Google Scholar] [CrossRef] [Green Version]
- Miyazaki, M.; Ntambi, J.M. Role of stearoyl-coenzyme A desaturase in lipid metabolism. Prostaglandins Leukot Essent Fat. Acids 2003, 68, 113–121. [Google Scholar] [CrossRef]
- Masuda, M.; Miyazaki-Anzai, S.; Keenan, A.L.; Okamura, K.; Kendrick, J.; Chonchol, M.; Offermanns, S.; Ntambi, J.M.; Kuro, O.M.; Miyazaki, M. Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity. J. Clin. Investig. 2015, 125, 4544–4558. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zong, G.; Li, Y.; Wanders, A.J.; Alssema, M.; Zock, P.L.; Willett, W.C.; Hu, F.B.; Sun, Q. Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: Two prospective longitudinal cohort studies. BMJ 2016, 355, i5796. [Google Scholar] [CrossRef] [Green Version]
- Praagman, J.; Vissers, L.E.T.; Mulligan, A.A.; Laursen, A.S.D.; Beulens, J.W.J.; van der Schouw, Y.T.; Wareham, N.J.; Hansen, C.P.; Khaw, K.-T.; Jakobsen, M.U.; et al. Consumption of individual saturated fatty acids and the risk of myocardial infarction in a UK and a Danish cohort. Int. J. Cardiol. 2019, 279, 18–26. [Google Scholar] [CrossRef] [Green Version]
- Brodeur, M.R.; Bouvet, C.; Barrette, M.; Moreau, P. Palmitic acid increases medial calcification by inducing oxidative stress. J. Vasc. Res. 2013, 50, 430–441. [Google Scholar] [CrossRef]
- Henriksbo, B.D.; Tamrakar, A.K.; Xu, J.; Duggan, B.M.; Cavallari, J.F.; Phulka, J.; Stampfli, M.R.; Ashkar, A.A.; Schertzer, J.D. Statins Promote Interleukin-1β-Dependent Adipocyte Insulin Resistance Through Lower Prenylation, Not Cholesterol. Diabetes 2019, 68, 1441–1448. [Google Scholar] [CrossRef]
- Awan, Z.; Denis, M.; Roubtsova, A.; Essalmani, R.; Marcinkiewicz, J.; Awan, A.; Gram, H.; Seidah, N.G.; Genest, J. Reducing Vascular Calcification by Anti-IL-1β Monoclonal Antibody in a Mouse Model of Familial Hypercholesterolemia. Angiology 2016, 67, 157–167. [Google Scholar] [CrossRef]
- Ridker, P.M.; Everett, B.M.; Thuren, T.; MacFadyen, J.G.; Chang, W.H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S.D.; et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N. Engl. J. Med. 2017, 377, 1119–1131. [Google Scholar] [CrossRef] [PubMed]
- Morin, C.; Blier, P.U.; Fortin, S. Eicosapentaenoic acid and docosapentaenoic acid monoglycerides are more potent than docosahexaenoic acid monoglyceride to resolve inflammation in a rheumatoid arthritis model. Arthritis Res. Ther. 2015, 17, 142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takase, O.; Hishikawa, K.; Kamiura, N.; Nakakuki, M.; Kawano, H.; Mizuguchi, K.; Fujita, T. Eicosapentaenoic acid regulates IκBα and prevents tubulointerstitial injury in kidney. Eur. J. Pharmacol. 2011, 669, 128–135. [Google Scholar] [CrossRef] [PubMed]
- Nishio, R.; Shinke, T.; Otake, H.; Nakagawa, M.; Nagoshi, R.; Inoue, T.; Kozuki, A.; Hariki, H.; Osue, T.; Taniguchi, Y.; et al. Stabilizing effect of combined eicosapentaenoic acid and statin therapy on coronary thin-cap fibroatheroma. Atherosclerosis 2014, 234, 114–119. [Google Scholar] [CrossRef] [PubMed]
- Niki, T.; Wakatsuki, T.; Yamaguchi, K.; Taketani, Y.; Oeduka, H.; Kusunose, K.; Ise, T.; Iwase, T.; Yamada, H.; Soeki, T.; et al. Effects of the Addition of Eicosapentaenoic Acid to Strong Statin Therapy on Inflammatory Cytokines and Coronary Plaque Components Assessed by Integrated Backscatter Intravascular Ultrasound. Circ. J. 2016, 80, 450–460. [Google Scholar] [CrossRef] [Green Version]
- Watanabe, T.; Ando, K.; Daidoji, H.; Otaki, Y.; Sugawara, S.; Matsui, M.; Ikeno, E.; Hirono, O.; Miyawaki, H.; Yashiro, Y.; et al. A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins. J. Cardiol. 2017, 70, 537–544. [Google Scholar] [CrossRef] [Green Version]
- Budoff, M. Effect of Icosapent Ethyl on prgression of coronary atherosclerosis in patients with elevated tryglycerides on statin therapy: The EVAPORATE study. In Proceedings of the 2019 AHA Scientific Sessions, Philadelphia, PA, USA, 18 November 2019. [Google Scholar]
- Fredriksson, R.; Höglund, P.J.; Gloriam, D.E.; Lagerström, M.C.; Schiöth, H.B. Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives. FEBS Lett. 2003, 554, 381–388. [Google Scholar] [CrossRef]
- Oh, D.Y.; Talukdar, S.; Bae, E.J.; Imamura, T.; Morinaga, H.; Fan, W.; Li, P.; Lu, W.J.; Watkins, S.M.; Olefsky, J.M. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010, 142, 687–698. [Google Scholar] [CrossRef] [Green Version]
- Carracedo, M.; Artiach, G.; Witasp, A.; Clària, J.; Carlström, M.; Laguna-Fernandez, A.; Stenvinkel, P.; Bäck, M. The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification. Cardiovasc. Res. 2018, 115, 1557–1566. [Google Scholar] [CrossRef] [Green Version]
- Arita, M.; Bianchini, F.; Aliberti, J.; Sher, A.; Chiang, N.; Hong, S.; Yang, R.; Petasis, N.A.; Serhan, C.N. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J. Exp. Med. 2005, 201, 713–722. [Google Scholar] [CrossRef]
- Carracedo, M.; Witasp, A.; Qureshi, A.R.; Laguna-Fernandez, A.; Brismar, T.; Stenvinkel, P.; Bäck, M. Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease. J. Intern. Med. 2019, 286, 449–457. [Google Scholar] [CrossRef]
Induction of Arterial Calcification | Species | In Vivo or In Vitro | Suppression of Calcification | Mechanisms | Reference |
---|---|---|---|---|---|
Warfarin | Rat | in vivo | Aorta calcification | Suppression of macrophage infiltration, MCP-1 expression and MMP activity in the aorta. | [19] |
Klotho deficiency | Mouse | in vivo | Aorta calcification | Suppression of NOX activity inducing oxidative stress via activation of GPR120 signaling in aortic smooth muscle cells. | [18] |
Activation of Wnt signaling | Human | in vitro | Osteogenic change | Suppression of Wnt signaling via PPARγ in smooth muscle cells. | [78] |
Palmitic acid | Human | in vitro | Osteogenic change Mineralization | Suppression of NF-κB signaling via ACSL3 downregulation in aortic smooth muscle cells. | [79] |
Author | Year | Region | Study Patients | Group | EPA Dose | Evaluation Method | Duration | Effect on Calcification |
---|---|---|---|---|---|---|---|---|
Miyoshi et al. [26] | 2018 | Japan | Patients with Agatston score 1–999, LDL-C levels ≥140 mg/dL, and no history of atherosclerotic cardiovascular disease | Pitavastatin vs. Pitavastatin plus EPA | 1.8 g/day | CT | 12 months | No significant difference in annual percent changes in Agatston score and calcium volume score. |
Niki et al. [124] | 2016 | Japan | Statin-treated patients with stable angina scheduled to be treated with PCI | Statin vs. Stain plus EPA | 1.8 g/day | IVUS | 6 months | No significant difference in percent change in calcium volume. |
Watanabe et al. [125] | 2017 | Japan | Patients with hypercholesterolemia, stable angina or acute coronary syndrome who have received successful PCI with IVUS guidance | Pitavastatin vs. Pitavastatin plus EPA | 1.8 g/day | IVUS | 6–8 months | No significant difference in calcium volume in non-stenting lesions. |
Budoff et al. [11] | ongoing | USA | Statin-treated patients with coronary atherosclerosis, fasting triglyceride levels of 135 to 499 mg/dL, and LDL-C levels of 40 to 115 mg/dL. | Statin vs. Stain plus EPA | 4 g/day | CT | 18 months | ongoing |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Saito, Y.; Nakamura, K.; Ito, H. Effects of Eicosapentaenoic Acid on Arterial Calcification. Int. J. Mol. Sci. 2020, 21, 5455. https://doi.org/10.3390/ijms21155455
Saito Y, Nakamura K, Ito H. Effects of Eicosapentaenoic Acid on Arterial Calcification. International Journal of Molecular Sciences. 2020; 21(15):5455. https://doi.org/10.3390/ijms21155455
Chicago/Turabian StyleSaito, Yukihiro, Kazufumi Nakamura, and Hiroshi Ito. 2020. "Effects of Eicosapentaenoic Acid on Arterial Calcification" International Journal of Molecular Sciences 21, no. 15: 5455. https://doi.org/10.3390/ijms21155455