Not All “BAD” Cholesterol Carriers Are Necessarily Bad and Not All “GOOD” Cholesterol Carriers Are as Good as Can Be: Plasma Delipidation, a Non-Pharmacological Treatment for Atherosclerosis
Author(s)
Bill Cham
ABSTRACT
More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone of reducing low-density lipoprotein-cholesterol, but despite significant clinical efficacy in the majority of patients, a large number of patients suffer from side effects and cannot tolerate the required statin dose to reach their recommended low-density lipoprotein-cholesterol goals. Preliminary clinical studies indicate that monoclonal antibodies to PCSK9 appear to be highly efficacious in lowering low-density lipoprotein-cholesterol with a favourable adverse event profile. However, further longer-term clinical studies are required to determine their safety. From the early-proposed concept for high-density lipoprotein-mediated cholesterol efflux for the treatment of coronary artery disease, the concentration of the cholesterol content in high-density lipoprotein particles has been considered a surrogate measurement for the efficacy of the reverse cholesterol transport process. However, unlike the beneficial effects of the statins and monoclonal antibodies to PCSK9 in reducing low-density lipoprotein-cholesterol, no significant advances have been made to increase the levels of high-density lipoprotein-cholesterol. Here it is shown that by a non-pharmacological plasma delipidation means, the atherogenic low-density lipoproteins can be converted to anti-atherogenic particles and that the high-density lipoproteins are converted to particles with extreme high affinity to cause rapid regression of atherosclerosis.
More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone of reducing low-density lipoprotein-cholesterol, but despite significant clinical efficacy in the majority of patients, a large number of patients suffer from side effects and cannot tolerate the required statin dose to reach their recommended low-density lipoprotein-cholesterol goals. Preliminary clinical studies indicate that monoclonal antibodies to PCSK9 appear to be highly efficacious in lowering low-density lipoprotein-cholesterol with a favourable adverse event profile. However, further longer-term clinical studies are required to determine their safety. From the early-proposed concept for high-density lipoprotein-mediated cholesterol efflux for the treatment of coronary artery disease, the concentration of the cholesterol content in high-density lipoprotein particles has been considered a surrogate measurement for the efficacy of the reverse cholesterol transport process. However, unlike the beneficial effects of the statins and monoclonal antibodies to PCSK9 in reducing low-density lipoprotein-cholesterol, no significant advances have been made to increase the levels of high-density lipoprotein-cholesterol. Here it is shown that by a non-pharmacological plasma delipidation means, the atherogenic low-density lipoproteins can be converted to anti-atherogenic particles and that the high-density lipoproteins are converted to particles with extreme high affinity to cause rapid regression of atherosclerosis.
Cite this paper
Cham, B. (2015) Not All “BAD” Cholesterol Carriers Are Necessarily Bad and Not All “GOOD” Cholesterol Carriers Are as Good as Can Be: Plasma Delipidation, a Non-Pharmacological Treatment for Atherosclerosis. International Journal of Clinical Medicine, 6, 690-699. doi: 10.4236/ijcm.2015.69092.
Cham, B. (2015) Not All “BAD” Cholesterol Carriers Are Necessarily Bad and Not All “GOOD” Cholesterol Carriers Are as Good as Can Be: Plasma Delipidation, a Non-Pharmacological Treatment for Atherosclerosis. International Journal of Clinical Medicine, 6, 690-699. doi: 10.4236/ijcm.2015.69092.
References
[1] Kannel, W.B., Castelli, W.P., Gordon, T. and McNamara, P.M. (1971) Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease: The Framingham Study. Annals of Internal Medicine, 74, 1-12.
http://dx.doi.org/10.7326/0003-4819-74-1-1 [2] Glomset, J.A. and Wright, J.L. (1964) Some Properties of a Cholesterol Esterifying Enzyme in Human Plasma. Biochimica et Biophysica Acta, 89, 266-276.
http://dx.doi.org/10.1016/0926-6569(64)90215-9 [3] Glomset, J.A. (1968) The Plasma Lecithins: Cholesterol Acyltransferase Reaction. Journal of Lipid Research, 9, 155-167. [4] Cham, B.E. and Knowles, B.R. (1976) A Solvent System for Delipidation of Plasma or Serum without Protein Precipitation. Journal of Lipid Research, 17, 176-181. [5] Cham, B.E. and Knowles, B.R. (1976) Changes in Electrophoretic Mobilities of Alpha and Beta Lipoproteins as a Result of Plasma Delipidation. Clinical Chemistry, 22, 305-309. [6] Cham, B.E. and Knowles, B.R. (1976) In Vitro Partial Relipidation of Apolipoproteins in Plasma. The Journal of Biological Chemistry, 251, 6367-6371. [7] Cham, B.E. and Chase, T.R. (2013) Intravascular Infusion of Autologous Delipidated Plasma Induces Antiatherogenic Lipoproteins and Causes Regression of Atherosclerosis—Studies in Non-Primates, Monkeys and Humans. Health (Special Issue on Atherosclerosis in Cardiovascular Disease), 5, 19-33. [8] Wong, C.G. and Ladisch, S. (1983) Retention of Gangliosides in Serum Delipidated by Diisopropyl Ether-Butanol Extraction. Journal of Lipid Research, 24, 666-669. [9] Cham, B.E. (2007) Manipulation of Reverse Cholesterol Transport System—An Exploration for Rapid Regression of Atherosclerosis. Research Journal of Biological Sciences, 2, 291-300. [10] Groener J.E.M., Van Rozen, A.E. and Erkelens, D.W. (1984) Cholesteryl Ester Transfer Activity. Localization and Role in the Distribution of Cholesteryl Ester among Lipoproteins in Man. Atherosclerosis, 50, 261-271.
http://dx.doi.org/10.1016/0021-9150(84)90074-1 [11] Groener, J.E.M., Pelton, R.W. and Kostner, G.M. (1986) Improved Estimation of Cholesteryl Ester Transfer/Exchange Activity in Serum or Plasma. Clinical Chemistry, 32, 283-286. [12] Innerarity, T.L. and Mahley, R.W. (1978) Enhanced Binding by Cultured Human Fibroblasts of Apo-E-Containing Lipoproteins as Compared with Low Density Lipoproteins. Biochemistry, 17, 1440-1447.
http://dx.doi.org/10.1021/bi00601a013 [13] Shakespeare, V. and Postle, A.D. (1979) Regulation of Cholesterol Synthesis in Skin Fibroblasts Derived from Old People. Atherosclerosis, 33, 359-364.
http://dx.doi.org/10.1016/0021-9150(79)90187-4 [14] Slater, H.R., Smith, E.B. and Roberston, F.W. (1980) The Effect of Delipidated High-Density Lipoprotein on Human Leukocyte Sterol Synthesis. Atherosclerosis, 35, 41-49.
http://dx.doi.org/10.1016/0021-9150(80)90026-X [15] Slater, H.R. and Robertson, F.W. (1979) A Comparison of Delipidated Sera Used in Studies of Sterol Synthesis by Human Mononuclear Lenkocytes. Journal Lipid Research, 20, 413-416. [16] Cham, B.E., Kostner, K.M., Dwivedy, A.K., Shafey, T.M., Fang, N.X. and Mahon, M.G. (1995) Lipid Apheresis: An in Vivo Application of Plasma Delipidation with Organic Solvents Resulting in Acute Transient Reduction of Circulating Plasma Lipids in Animals. Journal of Clinical Apheresis, 10, 61-69.
http://dx.doi.org/10.1002/jca.2920100202 [17] Cham, B.E., Kostner, K.M., Dwivedy, A.K., Shafey, T.M., Fang, N.X. and Mahon, M.G. (1996) Lipid Apheresis in an Animal Model Causes in Vivo Changes in Lipoprotein Electrophoretic Patterns. Journal of Clinical Apheresis, 11, 61-70.
http://dx.doi.org/10.1002/(SICI)1098-1101(1996)11:2<61::AID-JCA2>3.0.CO;2-8 [18] Kostner, K.M., Smith, J.L., Dwivedy, A.K., Shafey, T.M., et al. (1997) Lecithin Cholesterol Acyltransferase Activity in Normocholesterolemic and Hypercholesterolemic Roosters: Modulation by Lipid Apheresis. European Journal of Clinical Investigation, 27, 212-218.
http://dx.doi.org/10.1046/j.1365-2362.1997.960643.x [19] Groener, J.E.M., Van Rozen, A.E. and Erkelens, D.W. (1984) Cholesteryl Ester Transfer Activity: Localization and Role in the Distribution of Cholesteryl Ester among Lipoproteins in Man. Atherosclerosis, 50, 261-271.
http://dx.doi.org/10.1016/0021-9150(84)90074-1 [20] Cham, B.E., Kostner, K.M., Shafey, T.M., Smith, J.L. and Colquhoun, D.M. (2005) Plasma Delipidation Process Induces Rapid Regression of Atherosclerosis and Mobilization of Adipose Tissue. Journal of Clinical Apheresis, 20, 143-153.
http://dx.doi.org/10.1002/jca.20060 [21] Cham, B.E. and Smith, J.L. (1994) Lipid Apheresis in an Animal Model Causes Acute Reduction in Plasma Lipid Concentrations and Mobilization of Lipid from Liver and Aorta. Pharmacology Life Science Advances, 13, 25-32. [22] Cham, B.E. (1990) Autologous Plasma Delipidation Using a Continuous Flow System. US Patent No.: 4895558A. [23] Cham, B.E., Kostner, K.M., Colquhoun, D.M. and Dwivedy, A.K. (1994) Lipid-Apheresis: An in Vivo Application of Delipidation but Apo Lipoprotein Retention in Plasma of Calves by a Continuous Extracorporeal Procedure. Atherosclerosis, 109, 158.
http://dx.doi.org/10.1016/0021-9150(94)93644-7 [24] Cham, B.E., Kostner, K.M., Colquhoun, D.M. and Dwivedy, A.K. (1994) Lipid-Apheresis: An in Vivo Application of Delipidation but Apo Lipoprotein Retention in Plasma of Pigs by a Continuous Extracorporeal Procedure. Atherosclerosis, 109,159.
http://dx.doi.org/10.1016/0021-9150(94)93645-5 [25] Sacks, F.M., Rudel, L.L., Conner, A., Keefe, A., Kostner, G., Baki, T., et al. (2009) Selective Delipidation of Plasma HDL Enhances Reverse Cholesterol Transport in Vivo. Journal of Lipid Research, 50, 894-907.
http://dx.doi.org/10.1194/jlr.M800622-JLR200 [26] Waksman, R., Torguson, R., Kent, K.M., Pichard, A.D., Suddath, W.O., Satler, L.F., et al. (2010) A First-in-Man, Randomized, Placebo-Controlled Study to Evaluate the Safety and Feasibility of Autologous Delipidated High-Density Lipoprotein Plasma Infusions in Patients with Acute Coronary Syndrome. Journal of the American College Cardiology, 55, 2727-2735.
http://dx.doi.org/10.1016/j.jacc.2009.12.067 [27] Nissen, S.E., Tsunoda, T., Tuzcu, E.M., Schoenhagen, P., et al. (2003) Effect of Recombinant Apo A-I Milano on Coronary Atherosclerosis in Patients with Acute Coronary Syndromes. A Randomized Controlled Trial. JAMA, 290, 2292-2300.
http://dx.doi.org/10.1001/jama.290.17.2292
[1] Kannel, W.B., Castelli, W.P., Gordon, T. and McNamara, P.M. (1971) Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease: The Framingham Study. Annals of Internal Medicine, 74, 1-12.
http://dx.doi.org/10.7326/0003-4819-74-1-1 [2] Glomset, J.A. and Wright, J.L. (1964) Some Properties of a Cholesterol Esterifying Enzyme in Human Plasma. Biochimica et Biophysica Acta, 89, 266-276.
http://dx.doi.org/10.1016/0926-6569(64)90215-9 [3] Glomset, J.A. (1968) The Plasma Lecithins: Cholesterol Acyltransferase Reaction. Journal of Lipid Research, 9, 155-167. [4] Cham, B.E. and Knowles, B.R. (1976) A Solvent System for Delipidation of Plasma or Serum without Protein Precipitation. Journal of Lipid Research, 17, 176-181. [5] Cham, B.E. and Knowles, B.R. (1976) Changes in Electrophoretic Mobilities of Alpha and Beta Lipoproteins as a Result of Plasma Delipidation. Clinical Chemistry, 22, 305-309. [6] Cham, B.E. and Knowles, B.R. (1976) In Vitro Partial Relipidation of Apolipoproteins in Plasma. The Journal of Biological Chemistry, 251, 6367-6371. [7] Cham, B.E. and Chase, T.R. (2013) Intravascular Infusion of Autologous Delipidated Plasma Induces Antiatherogenic Lipoproteins and Causes Regression of Atherosclerosis—Studies in Non-Primates, Monkeys and Humans. Health (Special Issue on Atherosclerosis in Cardiovascular Disease), 5, 19-33. [8] Wong, C.G. and Ladisch, S. (1983) Retention of Gangliosides in Serum Delipidated by Diisopropyl Ether-Butanol Extraction. Journal of Lipid Research, 24, 666-669. [9] Cham, B.E. (2007) Manipulation of Reverse Cholesterol Transport System—An Exploration for Rapid Regression of Atherosclerosis. Research Journal of Biological Sciences, 2, 291-300. [10] Groener J.E.M., Van Rozen, A.E. and Erkelens, D.W. (1984) Cholesteryl Ester Transfer Activity. Localization and Role in the Distribution of Cholesteryl Ester among Lipoproteins in Man. Atherosclerosis, 50, 261-271.
http://dx.doi.org/10.1016/0021-9150(84)90074-1 [11] Groener, J.E.M., Pelton, R.W. and Kostner, G.M. (1986) Improved Estimation of Cholesteryl Ester Transfer/Exchange Activity in Serum or Plasma. Clinical Chemistry, 32, 283-286. [12] Innerarity, T.L. and Mahley, R.W. (1978) Enhanced Binding by Cultured Human Fibroblasts of Apo-E-Containing Lipoproteins as Compared with Low Density Lipoproteins. Biochemistry, 17, 1440-1447.
http://dx.doi.org/10.1021/bi00601a013 [13] Shakespeare, V. and Postle, A.D. (1979) Regulation of Cholesterol Synthesis in Skin Fibroblasts Derived from Old People. Atherosclerosis, 33, 359-364.
http://dx.doi.org/10.1016/0021-9150(79)90187-4 [14] Slater, H.R., Smith, E.B. and Roberston, F.W. (1980) The Effect of Delipidated High-Density Lipoprotein on Human Leukocyte Sterol Synthesis. Atherosclerosis, 35, 41-49.
http://dx.doi.org/10.1016/0021-9150(80)90026-X [15] Slater, H.R. and Robertson, F.W. (1979) A Comparison of Delipidated Sera Used in Studies of Sterol Synthesis by Human Mononuclear Lenkocytes. Journal Lipid Research, 20, 413-416. [16] Cham, B.E., Kostner, K.M., Dwivedy, A.K., Shafey, T.M., Fang, N.X. and Mahon, M.G. (1995) Lipid Apheresis: An in Vivo Application of Plasma Delipidation with Organic Solvents Resulting in Acute Transient Reduction of Circulating Plasma Lipids in Animals. Journal of Clinical Apheresis, 10, 61-69.
http://dx.doi.org/10.1002/jca.2920100202 [17] Cham, B.E., Kostner, K.M., Dwivedy, A.K., Shafey, T.M., Fang, N.X. and Mahon, M.G. (1996) Lipid Apheresis in an Animal Model Causes in Vivo Changes in Lipoprotein Electrophoretic Patterns. Journal of Clinical Apheresis, 11, 61-70.
http://dx.doi.org/10.1002/(SICI)1098-1101(1996)11:2<61::AID-JCA2>3.0.CO;2-8 [18] Kostner, K.M., Smith, J.L., Dwivedy, A.K., Shafey, T.M., et al. (1997) Lecithin Cholesterol Acyltransferase Activity in Normocholesterolemic and Hypercholesterolemic Roosters: Modulation by Lipid Apheresis. European Journal of Clinical Investigation, 27, 212-218.
http://dx.doi.org/10.1046/j.1365-2362.1997.960643.x [19] Groener, J.E.M., Van Rozen, A.E. and Erkelens, D.W. (1984) Cholesteryl Ester Transfer Activity: Localization and Role in the Distribution of Cholesteryl Ester among Lipoproteins in Man. Atherosclerosis, 50, 261-271.
http://dx.doi.org/10.1016/0021-9150(84)90074-1 [20] Cham, B.E., Kostner, K.M., Shafey, T.M., Smith, J.L. and Colquhoun, D.M. (2005) Plasma Delipidation Process Induces Rapid Regression of Atherosclerosis and Mobilization of Adipose Tissue. Journal of Clinical Apheresis, 20, 143-153.
http://dx.doi.org/10.1002/jca.20060 [21] Cham, B.E. and Smith, J.L. (1994) Lipid Apheresis in an Animal Model Causes Acute Reduction in Plasma Lipid Concentrations and Mobilization of Lipid from Liver and Aorta. Pharmacology Life Science Advances, 13, 25-32. [22] Cham, B.E. (1990) Autologous Plasma Delipidation Using a Continuous Flow System. US Patent No.: 4895558A. [23] Cham, B.E., Kostner, K.M., Colquhoun, D.M. and Dwivedy, A.K. (1994) Lipid-Apheresis: An in Vivo Application of Delipidation but Apo Lipoprotein Retention in Plasma of Calves by a Continuous Extracorporeal Procedure. Atherosclerosis, 109, 158.
http://dx.doi.org/10.1016/0021-9150(94)93644-7 [24] Cham, B.E., Kostner, K.M., Colquhoun, D.M. and Dwivedy, A.K. (1994) Lipid-Apheresis: An in Vivo Application of Delipidation but Apo Lipoprotein Retention in Plasma of Pigs by a Continuous Extracorporeal Procedure. Atherosclerosis, 109,159.
http://dx.doi.org/10.1016/0021-9150(94)93645-5 [25] Sacks, F.M., Rudel, L.L., Conner, A., Keefe, A., Kostner, G., Baki, T., et al. (2009) Selective Delipidation of Plasma HDL Enhances Reverse Cholesterol Transport in Vivo. Journal of Lipid Research, 50, 894-907.
http://dx.doi.org/10.1194/jlr.M800622-JLR200 [26] Waksman, R., Torguson, R., Kent, K.M., Pichard, A.D., Suddath, W.O., Satler, L.F., et al. (2010) A First-in-Man, Randomized, Placebo-Controlled Study to Evaluate the Safety and Feasibility of Autologous Delipidated High-Density Lipoprotein Plasma Infusions in Patients with Acute Coronary Syndrome. Journal of the American College Cardiology, 55, 2727-2735.
http://dx.doi.org/10.1016/j.jacc.2009.12.067 [27] Nissen, S.E., Tsunoda, T., Tuzcu, E.M., Schoenhagen, P., et al. (2003) Effect of Recombinant Apo A-I Milano on Coronary Atherosclerosis in Patients with Acute Coronary Syndromes. A Randomized Controlled Trial. JAMA, 290, 2292-2300.
http://dx.doi.org/10.1001/jama.290.17.2292