The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential
Jean-Charles Fruchart
(1)
,
Raul D. Santos
(2, 3)
,
Carlos Aguilar-Salinas
(4, 5)
,
Masanori Aikawa
(6)
,
Khalid Al Rasadi
(7)
,
Pierre Amarenco
(8)
,
Philip J. Barter
(9)
,
Richard Ceska
(10)
,
Alberto Corsini
(11)
,
Jean-Pierre Després
(12)
,
Patrick Duriez
(13)
,
Robert H. Eckel
(14)
,
Marat V. Ezhov
(15)
,
Michel Farnier
(16)
,
Henry N. Ginsberg
(17)
,
Michel P. Hermans
(18, 19)
,
Shun Ishibashi
(20)
,
Fredrik Karpe
(21, 22)
,
Tatsuhiko Kodama
(23)
,
Wolfgang Koenig
(24, 25, 26)
,
Michel Krempf
(27, 28, 29)
,
Soo Lim
(30, 31)
,
Alberto J. Lorenzatti
(32, 33)
,
Ruth Mcpherson
(34)
,
Jesus Millan Nuñez-Cortes
(35, 36, 37)
,
Børge G. Nordestgaard
(38, 39)
,
Hisao Ogawa
(40)
,
Chris J. Packard
(41)
,
Jorge Plutzky
(42)
,
Carlos I. Ponte-Negretti
(43)
,
Aruna Pradhan
(44, 6)
,
Kausik K. Ray
(45)
,
Zeljko Reiner
(46, 47)
,
Paul M. Ridker
(6, 48, 49)
,
Massimiliano Ruscica
(11)
,
Shaukat Sadikot
(50)
,
Hitoshi Shimano
(51)
,
Piyamitr Sritara
(52)
,
Jane K. Stock
(1)
,
Ta-Chen Su
(53)
,
Andrey V. Susekov
(54)
,
André Tartar
(55)
,
Marja-Riitta Taskinen
(56, 57)
,
Alexander Tenenbaum
(58, 59)
,
Lale S. Tokgözoğlu
(60)
,
Brian Tomlinson
(61)
,
Anne Tybjærg-Hansen
(39, 62, 38)
,
Paul Valensi
(63)
,
Michal Vrablik
(64, 10)
,
Walter Wahli
(65, 66, 67)
,
Gerald F. Watts
(68, 69)
,
Shizuya Yamashita
(70, 71)
,
Koutaro Yokote
(72)
,
Alberto Zambon
(73)
,
Peter Libby
(48, 6)
1
R3i Foundation
2 Hospital Israelita Albert Einstein [São Paulo, Brazil]
3 Lipid Clinic Heart Institute (InCor)
4 Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”
5 ITESM - Tecnológico de Monterrey = Monterrey Institute of Technology
6 Brigham and Women's Hospital [Boston]
7 SQU - Sultan Qaboos University
8 Department of Neurology
9 UNSW - University of New South Wales [Sydney]
10 General University Hospital in Prague
11 UNIMI - Università degli Studi di Milano = University of Milan
12 ULaval - Université Laval [Québec]
13 Université de Lille
14 University of Colorado Cancer Center [Aurora, CO, USA]
15 Russian Cardiology Research Center
16 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
17 Columbia University [New York]
18 Cliniques Universitaires Saint Luc
19 Institut de Recherche Expérimentale et Clinique (IREC)
20 Jichi Medical University [Tochigi-Ken, Japan]
21 University of Oxford
22 The Churchill hospital
23 UTokyo - The University of Tokyo
24 DHM - Deutsches Herzzentrum München
25 DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg
26 Universität Ulm - Ulm University [Ulm, Allemagne]
27 PhAN - Physiopathologie des Adaptations Nutritionnelles
28 Department of Endocrinology, Metabolic Diseases and Nutrition
29 Centre de recherche en nutrition humaine Ouest
30 SNUBH - Seoul National University Bundang Hospital
31 SNU - Seoul National University [Seoul]
32 Rusculleda Foundation for Research
33 Hospital Córdoba
34 University of Ottawa [Ottawa]
35 Hospital General Universitario "Gregorio Marañón"
36 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
37 Instituto de Investigaciones Sanitarias Gregorio Marañón
38 University Hospital Herlev Gentofte
39 Faculty of Health and Medical Sciences
40 NCCC - OSAKA - National Cerebral and Cardiovascular Center
41 Institute of Cardiovascular and Medical Sciences
42 Brigham and Women’s Hospital [Boston, MA]
43 Hospital El Pino
44 Boston University Medical Center
45 Imperial College London
46 School of Medicine
47 University Hospital Centre Zagreb
48 HMS - Harvard Medical School [Boston]
49 Massachusetts General Hospital
50 Jaslok Hospital & Research Centre
51 Université de Tsukuba = University of Tsukuba
52 Mahidol University [Bangkok]
53 National Taiwan University
54 Faculty of Clinical Pharmacology and Therapeutics
55 Faculté de Pharmacie
56 Clinical Research Institute HUCH
57 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
58 TAU - Tel Aviv University
59 Chaim Sheba Medical Center
60 Hacettepe University = Hacettepe Üniversitesi
61 Chinese University of Hong Kong
62 Copenhagen University Hospitals
63 Hôpital Jean Verdier [AP-HP]
64 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
65 ToxAlim - ToxAlim
66 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode
67 Lee Kong Chian School of Medicine
68 Royal Perth Hospital
69 UWA - The University of Western Australia
70 Medical Center
71 Osaka University
72 Chiba University
73 Department of Medicine (DIMED)
2 Hospital Israelita Albert Einstein [São Paulo, Brazil]
3 Lipid Clinic Heart Institute (InCor)
4 Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”
5 ITESM - Tecnológico de Monterrey = Monterrey Institute of Technology
6 Brigham and Women's Hospital [Boston]
7 SQU - Sultan Qaboos University
8 Department of Neurology
9 UNSW - University of New South Wales [Sydney]
10 General University Hospital in Prague
11 UNIMI - Università degli Studi di Milano = University of Milan
12 ULaval - Université Laval [Québec]
13 Université de Lille
14 University of Colorado Cancer Center [Aurora, CO, USA]
15 Russian Cardiology Research Center
16 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
17 Columbia University [New York]
18 Cliniques Universitaires Saint Luc
19 Institut de Recherche Expérimentale et Clinique (IREC)
20 Jichi Medical University [Tochigi-Ken, Japan]
21 University of Oxford
22 The Churchill hospital
23 UTokyo - The University of Tokyo
24 DHM - Deutsches Herzzentrum München
25 DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg
26 Universität Ulm - Ulm University [Ulm, Allemagne]
27 PhAN - Physiopathologie des Adaptations Nutritionnelles
28 Department of Endocrinology, Metabolic Diseases and Nutrition
29 Centre de recherche en nutrition humaine Ouest
30 SNUBH - Seoul National University Bundang Hospital
31 SNU - Seoul National University [Seoul]
32 Rusculleda Foundation for Research
33 Hospital Córdoba
34 University of Ottawa [Ottawa]
35 Hospital General Universitario "Gregorio Marañón"
36 UCM - Universidad Complutense de Madrid = Complutense University of Madrid [Madrid]
37 Instituto de Investigaciones Sanitarias Gregorio Marañón
38 University Hospital Herlev Gentofte
39 Faculty of Health and Medical Sciences
40 NCCC - OSAKA - National Cerebral and Cardiovascular Center
41 Institute of Cardiovascular and Medical Sciences
42 Brigham and Women’s Hospital [Boston, MA]
43 Hospital El Pino
44 Boston University Medical Center
45 Imperial College London
46 School of Medicine
47 University Hospital Centre Zagreb
48 HMS - Harvard Medical School [Boston]
49 Massachusetts General Hospital
50 Jaslok Hospital & Research Centre
51 Université de Tsukuba = University of Tsukuba
52 Mahidol University [Bangkok]
53 National Taiwan University
54 Faculty of Clinical Pharmacology and Therapeutics
55 Faculté de Pharmacie
56 Clinical Research Institute HUCH
57 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
58 TAU - Tel Aviv University
59 Chaim Sheba Medical Center
60 Hacettepe University = Hacettepe Üniversitesi
61 Chinese University of Hong Kong
62 Copenhagen University Hospitals
63 Hôpital Jean Verdier [AP-HP]
64 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
65 ToxAlim - ToxAlim
66 CIG - Center for Integrative Genomics - Institute of Bioinformatics, Génopode
67 Lee Kong Chian School of Medicine
68 Royal Perth Hospital
69 UWA - The University of Western Australia
70 Medical Center
71 Osaka University
72 Chiba University
73 Department of Medicine (DIMED)
Jean-Charles Fruchart
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Walter Wahli
- Fonction : Auteur
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Résumé
In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
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