Intercellular Adhesion Molecule 1 (ICAM‐1) Regulates Cardiac Remodeling and Function in Pressure Overload Induced Heart Failure

Left ventricular (LV) dysfunction and Heart Failure (HF) are associated in humans with systemic inflammation and elevated serum levels of intercellular cell adhesion molecule‐1 (ICAM‐1). ICAM‐1 regulates leukocyte recruitment into tissues, a process that in the heart can result in altered cardiac function. We hypothesized that endothelial ICAM‐1 regulates cardiac remodeling by controlling leukocyte recruitment to the heart. We used the mouse model of Thoracic Aortic Constriction (TAC) to induce cardiac remodeling and HF, combined with immunohistochemistry, flow cytometry, qPCR, echocardiography and hemodynamics. TAC induced up‐regulation of LV ICAM‐1 and LV T cell infiltration in WT mice. In contrast, CD3+ and CD4+ T cell recruitment into the LV was similar between ICAM‐1‐/‐ TAC and Sham mice. In response to TAC the systolic and diastolic functions were preserved in ICAM‐1‐/‐ mice, whereas LV weight, cardiomyocyte size, and mRNA expression of the hypertrophic markers ANP and BNP were decreased as compared to WT mice. In addition, TAC did not induce LV fibrosis or up‐regulation of the fibrotic markers Collagen‐I, TGFβ and SMAα in ICAM‐1‐/‐ mice. Our studies indicate that ICAM‐1 regulates LV T cell infiltration, cardiac function and fibrosis in HF induced by TAC. Further studies will determine the contribution of ICAM‐1 to HF pathogenesis via mediating T cell‐cardiac endothelium interactions or directly regulating cardiac cell function.