AIMS: The plasma level of interleukin-6 (IL-6) has been reported to be associated with left ventricular (LV) remodelling after myocardial infarction (MI). The present study was designed to examine whether anti-IL-6 receptor antibody (MR16-1) prevents the development of LV remodelling after MI. METHODS AND RESULTS: Balb/c male mice were subjected to MI by ligating the left anterior descending coronary artery. The mice were then treated with an intraperitoneal injection of MR16-1 (500 microg/body) or control IgG. MR16-1 decreased the myocardial myeloperoxidase activity and monocyte chemoattractant protein-1 concentration in the infarct region, concomitant with decreases in neutrophil and macrophage infiltration 3 days after ligation, while infarct size was comparable between the control IgG- and MR16-1-treated mice. At 7 days after ligation, MR16-1 significantly suppressed matrix metalloproteinase-2 activity in the infarct region. Furthermore, the MR16-1-treated mice demonstrated a reduction in LV dilatation and an improvement in LV contractile function compared with the control IgG-treated mice at 7 and 28 days after surgery, leading to an improvement in survival rate (80.6 vs. 59.5%, P < 0.05) at 28 days after surgery. The beneficial effects of MR16-1 were accompanied by histological suppression of cardiomyocyte hypertrophy and interstitial fibrosis in the non-infarct region. CONCLUSION: Administration of MR16-1 after MI suppressed myocardial inflammation, resulting in the amelioration of LV remodelling. Neutralization of the IL-6 receptor is a potentially useful strategy for protecting hearts from LV remodelling after MI.
AIMS: The plasma level of interleukin-6 (IL-6) has been reported to be associated with left ventricular (LV) remodelling after myocardial infarction (MI). The present study was designed to examine whether anti-IL-6 receptor antibody (MR16-1) prevents the development of LV remodelling after MI. METHODS AND RESULTS: Balb/c male mice were subjected to MI by ligating the left anterior descending coronary artery. The mice were then treated with an intraperitoneal injection of MR16-1 (500 microg/body) or control IgG. MR16-1 decreased the myocardial myeloperoxidase activity and monocyte chemoattractant protein-1 concentration in the infarct region, concomitant with decreases in neutrophil and macrophage infiltration 3 days after ligation, while infarct size was comparable between the control IgG- and MR16-1-treated mice. At 7 days after ligation, MR16-1 significantly suppressed matrix metalloproteinase-2 activity in the infarct region. Furthermore, the MR16-1-treated mice demonstrated a reduction in LV dilatation and an improvement in LV contractile function compared with the control IgG-treated mice at 7 and 28 days after surgery, leading to an improvement in survival rate (80.6 vs. 59.5%, P < 0.05) at 28 days after surgery. The beneficial effects of MR16-1 were accompanied by histological suppression of cardiomyocyte hypertrophy and interstitial fibrosis in the non-infarct region. CONCLUSION: Administration of MR16-1 after MI suppressed myocardial inflammation, resulting in the amelioration of LV remodelling. Neutralization of the IL-6 receptor is a potentially useful strategy for protecting hearts from LV remodelling after MI.
Authors: Matthew T Wolf; Yoram Vodovotz; Stephen Tottey; Bryan N Brown; Stephen F Badylak Journal: Tissue Eng Part C Methods Date: 2014-08-04 Impact factor: 3.056
Authors: Mateus D Marques; Victor Nauffal; Bharath Ambale-Venkatesh; Henrique D Vasconcellos; Colin Wu; Hossein Bahrami; Russell P Tracy; Mary Cushman; David A Bluemke; João A C Lima Journal: Hypertension Date: 2018-10 Impact factor: 10.190
Authors: Hugo L Paz Y Mar; Stanley L Hazen; Russell P Tracy; Kingman P Strohl; Dennis Auckley; James Bena; Lu Wang; Harneet K Walia; Sanjay R Patel; Reena Mehra Journal: Chest Date: 2016-03-18 Impact factor: 9.410