Tandem Mass Tag-Labeling Proteomics Reveals TLN1 as a Potential Factor in Cardiogenic Pulmonary Edema.

Abstract

Heart failure (HF) is a complex disease. The reduced blood flow associated with HF triggers the activation of neurohormonal systems, leading to symptoms such as pulmonary congestion and peripheral edema. The precise mechanisms responsible for edema in HF are poorly understood. In this study, we aimed to analyze the differentially expressed proteins in HF-induced pulmonary edema (HF-PE) and explore the potential underlying mechanisms. Proteins in the serum of patients with HF-PE (n = 10) and patients with HF without PE or those who have not developed PE yet (n = 10) were screened using tandem mass tag-labeling proteomics. The identified proteins were screened for differentially expressed proteins, which were then analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses as well as protein-protein interaction (PPI) visualization. Rats with HF were induced by myocardial infarction, whereas PE was induced by LPS. Finally, the rats were injected with lentiviruses to manipulate the expression of differentially expressed proteins. A total of 1796 proteins were identified. In the serum of patients with HF-PE, there were 143 significantly upregulated proteins and 147 significantly downregulated proteins. TLN1 interacted with multiple proteins and was upregulated in patients with HF-PE. TLN1 was significantly upregulated in the lung tissues of rats with HF-PE, and the progression of HF-PE was inhibited by TLN1 knockdown. This tandem mass tag-labeling proteomics profiling study revealed that TLN1 upregulation contributes to the progression of PE in patients with HF.