New developments in proprotein convertase subtilisin–kexin 9's biology and clinical implications
| Autor: | Nabil G. Seidah |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty animal structures Low-density lipoprotein receptor gene family Endocrinology Diabetes and Metabolism Induced Pluripotent Stem Cells 030204 cardiovascular system & hematology Biology 03 medical and health sciences chemistry.chemical_compound Proprotein Convertase Subtilisin/Kexin 9 0302 clinical medicine Downregulation and upregulation Internal medicine Genetics medicine Humans Disease Receptor Molecular Biology Triglycerides Nutrition and Dietetics Cholesterol PCSK9 fungi nutritional and metabolic diseases Cholesterol LDL Cell Biology Proprotein convertase 030104 developmental biology Endocrinology Receptors LDL chemistry LDL receptor Cancer research lipids (amino acids peptides and proteins) Proprotein Convertase 9 Cardiology and Cardiovascular Medicine |
| Zdroj: | Current Opinion in Lipidology. 27:274-281 |
| ISSN: | 0957-9672 |
| DOI: | 10.1097/mol.0000000000000295 |
| Popis: | High levels of LDL-cholesterol (LDL-C) are directly associated with devastating cardiovascular complications. Statins downregulate cholesterol synthesis and upregulate hepatic mRNA levels of LDL receptor (LDLR) and proprotein convertase subtilisin-kexin 9 (PCSK9), a validated enhancer of LDLR protein degradation. Herein, we summarize recent discoveries of the biological properties of PCSK9 in both health and disease states.PCSK9 downregulation of the LDLR protein likely explains the observed protective effect of the loss of PCSK9 in reducing lipoprotein(a) and incidence of septic shock. Injectable inhibitory PCSK9 monoclonal antibodies are now prescribed to hypercholesterolemic patients that do not reach target levels of LDL-C with available drugs. PCSK9 also reduces the levels of other receptors, for example, VLDL receptor (VLDLR), ApoER2, CD36, and CD81. The efficacy of the upregulation of LDLR and VLDLR cell surface levels in the absence of PCSK9 is both tissue and sex dependent. As LDLR, CD81, and VLDLR are hepatitis C receptors, PCSK9 may protect against certain viral infections.New functions of PCSK9 and other receptor targets are beginning to emerge to explain the observed changes in LDL-C and triglycerides. The effect of PCSK9 loss-of-function on glucose metabolism, factors that regulate the expression of PCSK9, and the roles of PCSK9 in other tissues, for example, intestine, kidney, and brain require further investigations. |
| Databáze: | OpenAIRE |
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