From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications

被引：30

作者：

Navarese, Eliano P. ^{[1
,2
]}

Kolodziejczak, Michalina ^{[1
,3
]}

Dimitroulis, Dimitrios ^{[1
,2
]}

Wolff, Georg ^{[1
,2
]}

Busch, Hans L. ^{[1
,2
]}

Devito, Fiorella ^{[1
,4
]}

Sionis, Alessandro ^{[5
]}

Ciccone, Marco Matteo ^{[1
,4
]}

机构：

[1] MED Res Network, SIRIO, Dusseldorf, Germany

[2] Univ Dusseldorf, Div Cardiol Pulmonol & Vasc Med, Dept Internal Med, Moorenstr 5, D-40225 Dusseldorf, Germany

[3] Univ Nicolaus Copernicus, Coll Med Bydgoszcz, Torun, Poland

[4] Univ Bari, DETO, Bari, Italy

[5] Hosp Santa Creu & Sant Pau, Dept Cardiol, Intens Cardiac Care Unit, Barcelona, Spain

来源：

EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY | 2016年 / 2卷 / 01期

关键词：

Proprotein convertase subtilisin; kexin type 9 (PCSK9); PCSK9; inhibitors; Clinical perspectives; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; EVOLOCUMAB AMG 145; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; PLASMA PCSK9 LEVELS; MONOCLONAL-ANTIBODY; LDL CHOLESTEROL; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; REDUCING LIPIDS;

D O I：

10.1093/ehjcvp/pvv045

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Statins are recommended as first-line therapy for patients with hypercholesterolaemia. A sizable proportion of patients, however, does not reach therapeutic goals, is statin intolerant, or, despite optimal statin therapy, is at high risk of ischaemic events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in lipid metabolism and several comorbidities. Monoclonal antibodies targeting PCSK9 are a new lipid-lowering approach with the potential to improve clinical outcomes in patients with dyslipidaemia. In this review, we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes. A state-of-the-art analysis of current clinical evidence and future directions on PCSK9 and its inhibition is provided.

引用

页码：44 / 53

页数：10

共 57 条

[1] Mutations in PCSK9 cause autosomal dominant hypercholesterolemia [J].

Abifadel, M ;

Varret, M ;

Rabès, JP ;

Allard, D ;

Ouguerram, K ;

Devillers, M ;

Cruaud, C ;

Benjannet, S ;

Wickham, L ;

Erlich, D ;

Derré, A ;

Villéger, L ;

Farnier, M ;

Beucler, I ;

Bruckert, E ;

Chambaz, J ;

Chanu, B ;

Lecerf, JM ;

Luc, G ;

Moulin, P ;

Weissenbach, J ;

Prat, A ;

Krempf, M ;

Junien, C ;

Seidah, NG ;

Boileau, C .

NATURE GENETICS, 2003, 34 (02) :154-156

[2] Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels [J].

Abujrad, H. ;

Mayne, J. ;

Ruzicka, M. ;

Cousins, M. ;

Raymond, A. ;

Cheesman, J. ;

Taljaard, M. ;

Sorisky, A. ;

Burns, K. ;

Ooi, T. C. .

ATHEROSCLEROSIS, 2014, 233 (01) :123-129

[3]

Allard Delphine, 2005, Hum Mutat, V26, P497, DOI 10.1002/humu.9383

[4] Circulating PCSK9 levels correlate with the serum LDL cholesterol level in newborn infants [J].

Araki, Shunsuke ;

Suga, Shutaro ;

Miyake, Fuyu ;

Ichikawa, Shun ;

Kinjo, Tadamune ;

Yamamoto, Yukiyo ;

Kusuhara, Koichi .

EARLY HUMAN DEVELOPMENT, 2014, 90 (10) :607-611

[5] PCSK9 levels in abdominally obese men: Association with cardiometabolic risk profile and effects of a one-year lifestyle modification program [J].

Arsenault, Benoit J. ;

Pelletier-Beaumont, Emilie ;

Almeras, Natalie ;

Tremblay, Angelo ;

Poirier, Paul ;

Bergeron, Jean ;

Despres, Jean-Pierre .

ATHEROSCLEROSIS, 2014, 236 (02) :321-326

[6] Regional Distribution and Metabolic Effect of PCSK9 insLEU and R46L Gene Mutations and apoE Genotype [J].

Awan, Zuhier ;

Delvin, Edgard E. ;

Levy, Emile ;

Genest, Jacques ;

Davignon, Jean ;

Seidah, Nabil G. ;

Baass, Alexis .

CANADIAN JOURNAL OF CARDIOLOGY, 2013, 29 (08) :927-933

[7] Rosuvastatin, Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations, and LDL Cholesterol Response: the JUPITER Trial [J].

Awan, Zuhier ;

Seidah, Nabil G. ;

MacFadyen, Jean G. ;

Benjannet, Suzanne ;

Chasman, Daniel I. ;

Ridker, Paul M. ;

Genest, Jacques .

CLINICAL CHEMISTRY, 2012, 58 (01) :183-189

[8] Plasma PCSK9 Is Associated with Age, Sex, and Multiple Metabolic Markers in a Population-Based Sample of Children and Adolescents [J].

Baass, Alexis ;

Dubuc, Genevieve ;

Tremblay, Michel ;

Delvin, Edgard E. ;

O'Loughlin, Jennifer ;

Levy, Emile ;

Davignon, Jean ;

Lambert, Marie .

CLINICAL CHEMISTRY, 2009, 55 (09) :1637-1645

[9] PCSK9 R46L, Low-Density Lipoprotein Cholesterol Levels, and Risk of Ischemic Heart Disease 3 Independent Studies and Meta-Analyses [J].

Benn, Marianne ;

Nordestgaard, Borge G. ;

Grande, Peer ;

Schnohr, Peter ;

Tybjaerg-Hansen, Anne .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 55 (25) :2833-2842

[10] A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia [J].

Blom, Dirk J. ;

Hala, Tomas ;

Bolognese, Michael ;

Lillestol, Michael J. ;

Toth, Phillip D. ;

Burgess, Lesley ;

Ceska, Richard ;

Roth, Eli ;

Koren, Michael J. ;

Ballantyne, Christie M. ;

Monsalvo, Maria Laura ;

Tsirtsonis, Kate ;

Kim, Jae B. ;

Scott, Rob ;

Wasserman, Scott M. ;

Stein, Evan A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (19) :1809-1819

← 1 2 3 4 5 6 →