The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: A multicenter FDG-PET trial

Atherosclerosis

Volumn 240, Issue 2, 2015, Pages 490-496

  Emami, Hamed ^a   Vucic, Esad ^a   Subramanian, Sharath ^a   Abdelbaky, Amr ^a   Fayad, Zahi A ^b   Du, Shuyan ^c   Roth, Eli ^d   Ballantyne, Christie M ^e   Mohler, Emile R ^f   Farkouh, Michael E ^g   Kim, Joonyoung ^c   Farmer, Matthew ^c   Li, Li ^c   Ehlgen, Alexander ^c   Langenickel, Thomas H ^c   Velasquez, Linda ^c   Hayes, Wendy ^c   Tawakol, Ahmed ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^c BRISTOL MYERS SQUIBB   (United States)

^d UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

^f HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA   (United States)

^g UNIVERSITY OF TORONTO   (Canada)

Author keywords

18FDG; Atherosclerosis; FDG; Hs CRP; Imaging; Inflammation; MAPK; PET; ROI; SUV; TBR

Indexed keywords

ANTIINFLAMMATORY AGENT; ATORVASTATIN; BMS 582949; C REACTIVE PROTEIN; FLUORODEOXYGLUCOSE F 18; GELATINASE B; HIGH DENSITY LIPOPROTEIN; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN; MEVINOLIN; MITOGEN ACTIVATED PROTEIN KINASE P38 INHIBITOR; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; 4-(5-(CYCLOPROPYLCARBAMOYL)-2-METHYLPHENYLAMINO)-5-METHYL-N-PROPYLPYRROLO(1,2-F)(1,2,4)TRIAZINE-6-CARBOXAMIDE; AUTACOID; BIOLOGICAL MARKER; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE P38; PROTEIN KINASE INHIBITOR; PYRROLE DERIVATIVE; RADIOPHARMACEUTICAL AGENT; TRIAZINE DERIVATIVE;

ADULT; AGED; ANGIOGRAPHY; ANTIINFLAMMATORY ACTIVITY; AORTA; ARTERY DISEASE; ARTERY INFLAMMATION; ARTICLE; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CAROTID ARTERY; COMPARATIVE STUDY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DRUG MEGADOSE; DRUG UPTAKE; DRUG WITHDRAWAL; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OPEN STUDY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; ANTAGONISTS AND INHIBITORS; AORTIC DISEASES; BLOOD; CAROTID ARTERY DISEASES; CLINICAL TRIAL; DIAGNOSTIC IMAGING; ENZYMOLOGY; INFLAMMATION; METABOLISM; MIDDLE AGED; MULTIMODAL IMAGING; PREDICTIVE VALUE; TIME FACTOR; TREATMENT OUTCOME; UNITED STATES; X-RAY COMPUTED TOMOGRAPHY;

AGED; ANTI-INFLAMMATORY AGENTS; AORTIC DISEASES; ATHEROSCLEROSIS; ATORVASTATIN CALCIUM; BIOMARKERS; C-REACTIVE PROTEIN; CAROTID ARTERY DISEASES; DOUBLE-BLIND METHOD; FEMALE; FLUORODEOXYGLUCOSE F18; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INFLAMMATION; INFLAMMATION MEDIATORS; MALE; MIDDLE AGED; MULTIMODAL IMAGING; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PLAQUE, ATHEROSCLEROTIC; POSITRON-EMISSION TOMOGRAPHY; PREDICTIVE VALUE OF TESTS; PROTEIN KINASE INHIBITORS; PYRROLES; RADIOPHARMACEUTICALS; TIME FACTORS; TOMOGRAPHY, X-RAY COMPUTED; TREATMENT OUTCOME; TRIAZINES; UNITED STATES;

EID: 84928251706     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2015.03.039     Document Type: Article

References (27)

1. Dahlöf B. Cardiovascular disease risk factors: epidemiology and risk assessment. Am. J. Cardiol. 2010, 105:3A-9A.
2. Crea F., Liuzzo G. Pathogenesis of acute coronary syndromes. J.Am. Coll. Cardiol. 2013, 61:1-11.
3. Ridker P.M., Cannon C.P., Morrow D., et al. C-Reactive protein levels and outcomes after statin therapy. N.Engl. J. Med. 2005, 352:20-28.
4. Nissen S.E., Tuzcu E.M., Schoenhagen P., et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N.Engl. J. Med. 2005, 352:29-38.
5. Rubenfire M., Brook R.D., Rosenson R.S. Treating mixed hyperlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events. Am. J. Med. 2010, 123:892-898.
6. Libby P. Inflammation in atherosclerosis. Nature 2002, 420:868-874.
7. Charo I.F., Taub R. Anti-inflammatory therapeutics for the treatment of atherosclerosis. Nat. Rev. Drug Discov. 2011, 10:365-376.
8. Muslin A.J. MAPK signalling in cardiovascular health and disease: molecular mechanisms and therapeutic targets. Clin. Sci. (Lond.) 2008, 115:203.
9. Kaminska B. MAPK signalling pathways as molecular targets for anti-inflammatory therapy-from molecular mechanisms to therapeutic benefits. Biochim.Biophys. Acta (BBA) - Proteins Proteomics 2005, 1754:253-262.
10. Cheriyan J., Webb A.J., Sarov-Blat L., et al. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation 2011, 123:515-523.
11. Proctor B.M., Jin X., Lupu T.S., Muglia L.J., Semenkovich C.F., Muslin A.J. Requirement for p38 mitogen-activated protein kinase activity in neointima formation after vascular injury. Circulation 2008, 118:658-666.
12. 18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002, 105:2708-2711.
13. 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J.Am. Coll. Cardiol. 2006, 48:1818-1824.
14. Tahara N., Kai H., Ishibashi M., et al. Simvastatin attenuates plaque inflammation. J.Am. Coll. Cardiol. 2006, 48:1825-1831.
15. Wu Y.-W., Kao H.-L., Huang C.-L., et al. The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers. Eur. J. Nucl. Med. Mol. Imaging 2011, 39:399-407.
16. Vucic E., Dickson S.D., Calcagno C., et al. Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging. JACC Cardiovasc. Imaging 2011, 4:1100-1109.
17. Vucic E., Calcagno C., Dickson S.D., et al. Regression of inflammation in atherosclerosis by the LXR agonist R211945. JACC Cardiovasc Imaging 2012, 5:819-828.
18. Mizoguchi M., Tahara N., Tahara A., et al. Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes. JACC Cardiovasc Imaging 2011, 4:1110-1118.
19. Elkhawad M., Rudd J.H.F., Sarov-Blat L., et al. Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients with atherosclerosis. JACC Cardiovasc Imaging 2012, 5:911-922.
20. Liu C., Lin J., Wrobleski S.T., et al. Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl- N-propylpyrrolo[1,2- f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP Kinase inhibitor for the treatment of inflammatory diseases. J.Med. Chem. 2010, 53:6629-6639.
21. 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J.Am. Coll. Cardiol. 2006, 48:1818-1824.
22. 18Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible. J.Am. Coll. Cardiol. 2007, 50:892-896.
23. Fayad Z.A., Mani V., Woodward M., et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet 2011, 378:1547-1559.
24. 18F-Fluorodeoxyglucose-PET imaging. J.Am. Coll. Cardiol. 2014, 63:86-88.
25. Seimon T.A., Wang Y., Han S., et al. Macrophage deficiency of p38α MAPK promotes apoptosis and plaque necrosis in advanced atherosclerotic lesions in mice. J.Clin. Investig. 2009, 119:886-898.
26. Kardakaris R., Gareus R., Xanthoulea S., Pasparakis M. Endothelial and macrophage-specific deficiency Of P38α MAPK does not affect the pathogenesis of atherosclerosis in ApoE-/- mice. PLoS One 2011, 6:e21055. Gaetano C.
27. Tawakol A., Fayad Z.A., Mogg R., et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of A multi-center FDG-PET/CT feasibility study. J.Am. Coll. Cardiol. 2013, 62:909-917.