Carbonic anhydrase 2 and 3 as risk biomarkers for dilated cardiomyopathy associated heart failure

Background: Dilated cardiomyopathy (DCM) is a complex type of cardiomyopathy that is affected by both genetic and non-genetic factors. It is characterized by an enlargement of the left ventricle or bi-ventricle, and is often accompanied by cardiac systolic dysfunction. The main results include arrhythmia, heart failure (HF), and sudden death. The prognosis of this disease is usually poor, and the 5-year survival time is about 50%. Early diagnosis is very important for the treatment of DCM. Studies have shown that primary prevention after discovering the disease effectively reduces the mortality rate of the disease. However, there is currently no effective biomarker for the early diagnosis of DCM. The rapid development of omics in protein has promoted the "precise" study of modern medical research. In this article, the potential biomarkers for predicting and diagnosing DCM-related HF were studied by a plasma protein omics analysis.

Methods: Tandem mass tag-labeled quantitative proteomic studies were performed in 20 patients, comprising 10 DCM-associated HF patients, and 10 control patients who without clinical HF events. Further validation research was conducted by enzyme-linked immunosorbent assay (ELISA) with an expanded cohort (control group =40; HF group =48).

Results: Among the 854 identified proteins, the expression of 86 proteins was significantly upregulated, while the expression of 21 proteins was downregulated (with an expression difference >1.5-fold; P<0.05) in the 2 groups. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction (PPI) networks analyses indicated that the bicarbonate transport process played a critical role in HF. Importantly, carbonic anhydrase 2 (CA2) and 3 (CA3), which play central roles in regulating the transport of bicarbonate, were highly expressed in the HF group. The ELISA validation results showed that the expression levels of CA2 and CA3 at admission were remarkably higher (P<0.0001 and P=0.0157) in the plasma of the HF patients than that of the control patients.

Conclusions: The present study showed that two molecules (i.e., CA2 and CA3) are involved in the bicarbonate transport pathway, and are risk factors and potential biomarkers for the diagnosis of DCM patients with HF.