Abstract
We have previously shown that cardiac sarcopenia occurs with age in C57/BL6J mice. However, underlying mechanisms and plasma biomarkers of cardiac aging have not been identified. Accordingly, the objective of this study is to evaluate plasma biomarkers that reflect cardiac aging phenotypes. Plasma from young (7.5 months, n=27) and senescent (31.8 months, n=25) C57/BL6J mice were collected and levels of 69 markers were measured by multi‐analyte profiling. Of these, 27 analytes were significantly higher in the senescent group. The majority were inflammatory markers associated with macrophage functions, including monocyte chemotactic protein‐1 (MCP‐1) and matrix metalloproteinase‐9 (MMP‐9). Immunoblotting showed higher MCP‐1 levels in left ventricle (LV) of senescent mice (p<0.05), and LV MCP‐1 levels correlated with plasma MCP‐1 levels (R=0.27, p<0.05). Both, immunoblotting of CD68 and immunohistochemistry for ER‐HR3 showed higher macrophage levels in the senescent LV. Further, the increased MCP‐1 and MMP‐9 levels correlated with the decrease in LV function in the senescent mice. In conclusion, this study suggests that MCP‐1 and MMP‐9 are potential plasma markers for cardiac aging and that augmented MCP‐1 and MMP‐9 levels and macrophage content in the LV could provide an underlying mechanism in cardiac aging. NSF 0649172 and NIH 1SC2 HL101430 to Y.J. and NIH R01 HL‐75360 and AHA 0855119F to M.L.L.
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