title: Suggestive evidence of a multi-cytokine resistin pathway in humans and its role on cardiovascular events in high-risk individuals.
abstract: In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine "resistin pathway". We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMAIR, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure data were available and in 353 patients with type 2 diabetes and coronary artery disease from the Gargano Heart Study (GHS)-prospective design (follow-up 5.4 ± 2.5 years; 71 MACE). In GS2, cytokines mRNA levels in white blood cells were also measured. In GS2, resistin mRNA was correlated with all cytokines expression (all p < 0.001), but IL-12B. Consistently, serum resistin was correlated with all serum cytokines (all p < 0.001), but IL-12. Expression (eRPS) and serum (sRPS) resistin pathway scores (excluding IL-12) were each other correlated (p < 0.001) and both associated with cardiovascular risk factors (all p < 0.01). In GHS, sRPS was independently associated with MACE (HR = 1.44, 95% CI = 1.10-1.90). Our data indicate the existence of a resistin pathway, which is associated with cardiovascular risk factors and which strongly and independently predicts MACE.
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Menzaghi
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Marucci
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Antonucci
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: De Bonis
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Ortega Moreno
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvemini
authors.affiliation: Unit of Biostatistics, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.|Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.affiliation: Research Unit of Diabetes and Endocrine Diseases, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Paola
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D052243:Resistin / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D055105:Waist Circumference
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; C499624:RETN protein, human; D052243:Resistin; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12