Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 pathways

Rao, Xiaoquan; Zhao, Shi; Braunstein, Zachary; Mao, Hong; Razavi, Michael; Duan, Lihua; Wei, Yingying; Toomey, Amelia C.; Rajagopalan, Sanjay; Zhong, Jixin

All procedures of this study were approved by the Institutional Review Board (IRB) at The Ohio State University and Case Western Reserve University. A written informed consent was obtained from all the participants before the study. A total of 27 patients with previously documented cardiovascular disease enrolled in the ALPINE trial were included in this study. The ALPINE, a phase 4 clinical trial (ClinicalTrials.gov Identifier: NCT01417104), has been described elsewhere [15] . Patients with established cardiovascular disease were recruited in Columbus, Ohio from 2009 to 2011 and randomized to receive either placebo or aliskiren treatment. Cardiovascular disease was defined as at least 1 of the following: myocardial infarction, cerebrovascular accident, previous coronary artery bypass graft surgery, and/or percutaneous coronary intervention or peripheral arterial disease (ankle-brachial index b0.9 and/or prior peripheral intervention or surgery). HOMA-IR was calculated as follows: HOMA-IR = Fasting Serum Glucose (mg/dL) × Fasting Plasma insulin (μU/mL) / 405. Patients with one or more of the following conditions were excluded from the study: history of malignancy, diagnosis of type 1 diabetes or use of hypoglycemic drugs, uncontrolled hypertension (N145/ 90 mmHg); renal insufficiency defined as glomerular filtration rate b 40 mL/min (derived with the Modified Diet in Renal Disease equation); unstable cardiac syndromes. Data from atherosclerotic patients within the placebo group were re-analyzed. Fourteen age-and racematched healthy volunteers without cardiovascular disease as defined above were served as controls.