Joint proteomic and metabolomic analysis reveals renal metabolic remodeling of chronic heart failure mice.

Pharmacologic intervention in chronic heart failure (HF) with renal insufficiency is one of the clinical challenges due to the fact that the mechanisms of cardio-renal interactions in chronic heart failure (CHF) progressing have not been fully revealed. In this paper, C57BL/6 mice were applied thoracic aortic narrowing surgery to establish pressure overload CHF model. Cardiac function, serum markers, renal pathologic changes and kidney metabolism were analyzed at 4th, 8th, 12th, and 16th week after surgery respectively to evaluate the heart-Kidney pathologic overlap. Kidney proteomic analysis was performed at 16th week after operation. As a result, renal hypofiltration and exacerbation of pathological damage was observed accompanying cardiac function deterioration after 12th week. 66 differentially expressed proteins and 13 differential metabolites were found to be involved in the cardio-renal pathological overlap. Joint proteomic and metabolomic analysis revealed that signal pathways like Phosphatidylinositol signaling system, Glucagon signaling pathway, the Glyoxylate and dicarboxylate metabolism; DEPs of Pten, Mtmr4, PLC and CPT1, differential metabolites like aspartic acid and isocitrate deserve further investigation.