Anti-PCSK9 Vaccines - An Emerging Therapeutic Innovative Game Changer in Dyslipidemia and Beyond
American Journal of Internal Medicine
Volume 8, Issue 6, November 2020, Pages: 250-253
Received: Sep. 23, 2020;
Accepted: Oct. 15, 2020;
Published: Oct. 26, 2020
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Mrinal Kanti Das, Department of Cardiology, C. K. Birla Hospitals, Kolkata, India
Tapan Sinha, Department of Cardiology, Kothari Medical Centre, Kolkata, India
Mahesh Kumar Chaudhary, Department of Cardiology, C. K. Birla Hospitals, Kolkata, India
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Proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) regulates the cholesterol metabolism by genetic mechanism mediating the LDL receptor degradation. Gain of the functions of the PCSK9 variants resulted in high level of LDL-cholesterol and loss of function in low level of the LDL-cholesterol level. The low level of LDL-cholesterol was associated with significant decrease in coronary artery disease. The genetic insight of lipid homeostasis and complex molecular biochemistry triggered a domain of active pharmacological research with prospect of introducing paradigm shift in primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in group of non-responders to anti-cholesterol treatment. The result has been the discovery of the PCSK9 inhibitors and vaccines. The former got the statutory approval by Federal Drug Administration (FDA) in conditions namely patients with heterozygous familial hypercholesterolemia (FH), individuals with ASCVD requiring further lowering of LDL-cholesterol levels. This has also important role in statin-intolerant patients. The various international guidelines have put the concept of the therapeutic approach in acute coronary syndrome (ACS) specially in high risk post-MI patients. However the present article will focus more on the PCSK9 vaccine and the encouraging evidences of its pleotropic effects in treatment of chronic clinical conditions and cancer. There are few challenges which need to be further explored especially considering the cost-benefit ratio. There is also the need of further research focusing on the expansion of the indications.
Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease (PCSK9), PCSK9 Inhibitors, Dyslipidemia and Beyond, Pleotropic Actions
To cite this article
Mrinal Kanti Das,
Mahesh Kumar Chaudhary,
Anti-PCSK9 Vaccines - An Emerging Therapeutic Innovative Game Changer in Dyslipidemia and Beyond, American Journal of Internal Medicine. Special Issue: Dyslipidemia: Flash Back and Vision Ahead.
Vol. 8, No. 6,
2020, pp. 250-253.
Copyright © 2020 Authors retain the copyright of this article.
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Warren, JB, et al. Cholesterol Trials and Mortality. Br J Clinical Pharmacol (2016) 82: 168-177.
Ray KK, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65 229 participants. Arch Intern Med 2010; 170: 1024–31.
Nakamura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 2006; 368: 1155–63.
Bulbulia R, et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 highrisk individuals: a randomised controlled trial. Lancet 2011; 378: 2013–20.
Waters DD, et al. (2009) Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation 120: 28–34.
Michael D. Shapiro et al. PCSK9: From Basic Science Discoveries to Clinical Trials. Circ Res. 2018 May 11; 122 (10): 1420–1438.
Cameron J, et al. (2006) Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 15: 1551–1558.
Yajie Pan et al. A Therapeutic Peptide Vaccine Against PCSK9. Nature.com/scientific reports. 7: 12534 | DOI: 10.1038/s41598-017-13069-w.
Chaudhhary R et al. PCSK9 Inhibitors: A new era of lipid lowering therapy. World J Cardiolo 2017 February 26; 9 (2): 76-91.
Kosmas Constantine E. et al. Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia. Diseases. 2018 Sep; 6 (3): 63.
Chen, X. et al. Efectiveness and Safety of a Terapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals. HYPERTENSION. 61, 408–416 (2013).
Ryo Kawakami et al. Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/ kexin type 9 (PCSK9) epitope in mice. https://doi.org/10.1371/journal.pone.0191895 February 13, 2018.
Amir Abbas Momtazi-Borojeni, et al. Effects of immunization against PCSK9 in an experimental model of breast cancer. Arch Med Sci 2019; 15 (3): 570–579.
Amir Abbas Momtazi-Borojeni, et al. Potential anti-tumor effect of a nanoliposomal antiPCSK9 vaccine in mice bearing colorectal cancer. Arch Med Sci 2019; 15 (3): 559–559.
Ridker PM, et al. Plasma proprotein convertase subtilisin/kexin type 9 levels and the risk of first cardiovascular events. Eur Heart J. 2016; 37: 554–60. [PubMed: 26508163].
Laugsand LE, et al. Circulating PCSK9 and Risk of Myocardial Infarction. JACC: Basic To Translational Science. 2016; 1: 568–575.
Li JJ, et al. Proprotein Convertase Subtilisin/Kexin type 9, C-Reactive Protein, Coronary Severity, and Outcomes in Patients With Stable Coronary Artery Disease: A Prospective Observational Cohort Study. Medicine (Baltimore). 2015; 94: e2426. [PubMed: 26717403].
Gencer B, et al. Prognostic value of PCSK9 levels in patients with acute coronary syndromes. Eur Heart J. 2016; 37: 546–53. [PubMed: 26655339].
Ravnskov U, et al. Lack of an association or an inverse association between low-densitylipoprotein cholesterol and mortality in the elderly: a systematic review. http://dx.doi.org/10.1136/bmjopen-2015-010401.