Absence of microRNA‐155 protects against pressure overload‐induced cardiac inflammation and failure

Cardiac hypertrophy, accompanied by progressive inflammation, and consequent heart failure (HF) continue to burden Western society. We show that miR‐155, a microRNA expressed by cardiac macrophages, stimulates the secretion of pro‐hypertrophic and ‐ inflammatory factors by macrophages and thereby causes adverse inflammation and HF. We subjected miR‐155 knockout (KO), wild type (WT) and antagomiR‐treated mice to pressure overload by angiotensin II or transverse aortic constriction to induce cardiac hypertrophy, inflammation and failure. Absence of miR‐155 inhibited the cardiac hypertrophic response and hampered cardiac macrophage activity. Bone marrow transplantation with miR‐155 KO and WT mice confirmed that miR‐155 in the macrophage mediates cardiac hypertrophy. It does so by repressing its direct target Suppressor of Cytokine Signalling‐1, leading to increased cytokine secretion and STAT3 activity, both implicated in cardiac inflammation and hypertrophy. These findings demonstrate the causative relation between inflammatory signalling and HF, and implicate microRNA‐155 as a therapeutic target in heart failure.