| First Author | Lynch TL 4th | Year | 2017 |
| Journal | J Mol Cell Cardiol | Volume | 102 |
| Pages | 83-93 | PubMed ID | 27955979 |
| Mgi Jnum | J:250964 | Mgi Id | MGI:6102254 |
| Doi | 10.1016/j.yjmcc.2016.12.002 | Citation | Lynch TL 4th, et al. (2017) Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation. J Mol Cell Cardiol 102:83-93 |
| abstractText | Cardiomyopathies are a leading cause of heart failure and are often caused by mutations in sarcomeric genes, resulting in contractile dysfunction and cellular damage. This may stimulate the production of a robust proinflammatory response. To determine whether myocardial inflammation is associated with cardiac dysfunction in dilated cardiomyopathy (DCM) caused by MYBPC3 mutation, we used the well-characterized cMyBP-C((t/t)) mouse model of DCM at 3months of age. Compared to wild type (WT) mice, DCM mice exhibited significantly decreased fractional shortening (36.4+/-2% vs. 15.5+/-1.0%, p<0.0001) and significantly increased spleen weight (5.3+/-0.3 vs. 7.2+/-0.4mg/mm, p=0.002). Intriguingly, flow cytometry analysis revealed a significant increase in total (CD45(+)CD11b(+)Ly6C(-)MHCII(+)F480(+)) macrophages (6.5+/-1.4% vs. 14.8+/-1.4%, p=0.002) and classically activated (CD45(+)CD11b(+)Ly6C(-)MHCII(+)F480(+)CD206(-)) proinflammatory (M1) macrophages (3.4+/-0.8% vs. 10.3+/-1.2%, p=0.0009) in DCM hearts as compared with WT hearts. These results were further confirmed by immunofluorescence analysis of heart tissue sections. Splenic red pulp (CD11b(+)Ly6C(+)MHCII(low)F480(hi)) macrophages were significantly elevated (1.3+/-0.1% vs. 2.4+/-0.1%, p=0.0001) in DCM compared to WT animals. Serum cytokine analysis in DCM animals exhibited a significant increase (0.65+/-0.2 vs. 2.175+/-0.5pg/mL, p=0.02) in interleukin (IL)-6 compared to WT animals. Furthermore, RNA-seq analysis revealed the upregulation of inflammatory pathways in the DCM hearts. Together, these data indicate a robust proinflammatory response in DCM hearts, likely in response to cellular damage triggered by MYBPC3 mutation and resultant contractile dysfunction. |
