CCR2 dependent recruited pro-inflammatory monocytes contribute to the development of left ventricular hypertrophy in mice upon transverse aortic constriction.

C-C chemokine receptor type 2 positive monocytes are recruited from the circulation to infiltrate inflamed tissue. Left ventricular (LV) hypertrophy caused by pressure overload presents with a chronic myocardial inflammation in our mouse model of transverse aortic constriction (TAC). Recent analyses demonstrated that deficiency of fractalkine receptor CX3CR1 leads to a pro-inflammatory phenotype characterized by increased numbers of Ly6Chigh macrophages in the myocardium due to chemokine receptor CCR2 dependent monocyte recruitment from the circulation. Here, we analyzed the role of CCR2 in the development of left ventricular hypertrophy using Ccr2-/- mice. We were able to show that a lack of CCR2 dependent recruited Ly6Chigh monocytes in the myocardium reveled cardioprotective effects resulting in less hypertrophy and reduced brain natriuretic peptide (BNP) expression, as biomarker of heart failure, in the myocardium. CCR2-deficiency caused an increase in neutrophil and a reduced macrophage accumulation in the myocardium in response to pressure overload. The cytokine pattern measured in the LV tissue indicates a significantly reduced release of IL1-β whereas TNF-α concentrations are increased following TAC. IL-6 secretion is not altered by the lack of CCR2 and the pro-remodeling cytokine IL-10 is not increased either. This study highlights the importance of CCR2 in the pathogenesis of LV hypertrophy and the relevance of CCR2 dependent recruited monocytes for the orchestration of the cardiac immune response.