title: Peroxisome proliferator-activated receptors (PPAR) downregulate the expression of pro-inflammatory molecules in an experimental model of myocardial infarction.
abstract: Myocardial infarction (MI) has been associated with an inflammatory response and a rise in TNF-α, interleukin (IL)-1β, and IL-6. Peroxisome proliferator-activated receptors (PPARs) promote a decreased expression of inflammatory molecules. We aimed to study whether PPAR stimulation by clofibrate decreases inflammation and reduces infarct size in rats with MI. Male Wistar rats were randomized into 3 groups: control, MI + vehicle, and MI + clofibrate (100 mg/kg). Treatment was administered for 3 consecutive days, previous to 2 h of MI. MI induced an increase in protein expression, mRNA content, and enzymatic activity of inducible nitric oxide synthase (iNOS). Additionally, MI incited an increased expression of matrix metalloproteinase (MMP)-2 and MMP-9, intercellular adhesion molecule (ICAM)-1, and IL-6. MI also elevated the nuclear content of nuclear factor-κB (NF-κB) and decreased IκB, both in myocyte nuclei and cytosol. Clofibrate treatment prevented MI-induced changes in iNOS, MMP-2 and MMP-9, ICAM-1, IL-6, NF-κB, and IκB. Infarct size was smaller in clofibrate-treated rats compared to MI-vehicle animals. In silico analysis exhibited 3 motifs shared by genes from renin-angiotensin system, PPARα, iNOS, MMP-2 and MMP-9, ICAM-1, and VCAM-1, suggesting a cross regulation. In conclusion, PPARα-stimulation prevents overexpression of pro-inflammatory molecules and preserves viability in an experimental model of acute MI.
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: María de la Luz
authors.initials: Mde L
authors.lastname: Ibarra-Lara
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Aguilar
authors.affiliation: b Department of Pathology, National Institute of Cardiology Ignacio Chávez, Mexico City, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Soria
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Torres-Narváez
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Del Valle-Mondragón
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: Luz Graciela
authors.initials: LG
authors.lastname: Cervantes-Pérez
authors.affiliation: c Department of Neurochemistry, National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez", Mexico City, Mexico.
authors.forename: Francisca
authors.initials: F
authors.lastname: Pérez-Severiano
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: Margarita Del Carmen
authors.initials: Mdel C
authors.lastname: Ramírez-Ortega
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pastelín-Hernández
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.|d Department of Pharmacobiology, Research and Advanced Studies Center of National Polytechnic Institute of Mexico, Mexico City, Mexico.
authors.forename: Víctor Hugo
authors.initials: VH
authors.lastname: Oidor-Chan
authors.affiliation: a Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 Mexico City, México.
authors.forename: Alicia
authors.initials: A
authors.lastname: Sánchez-Mendoza
mesh_terms: D000818:Animals; D002994:Clofibrate / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018836:Inflammation Mediators; D047493:PPAR alpha; D002994:Clofibrate
keywords: IκB; NF-κB; PPAR; cell adhesion molecules; fibrates; iNOS; infarctus du myocarde; interleukines; interleukins; matrix metalloproteinases; molécules d’adhésion intercellulaire; myocardial infarction; métalloprotéinases matricielles