Serum biomarker analysis at the protein level on pulmonary hypertension secondary to old anterior myocardial infarction

Abstract

Pulmonary hypertension (PH) related to old anterior myocardial infarction (OAMI) always accompanies a bad prognosis, and thus, we aimed to screen serum biomarkers related to PH in OAMI patients. According to right ventricular systolic pressure, we divided mice into sham, OAMI, and PH-OAMI groups and evaluated body, heart and lung weight, heart function, pulmonary blood flow velocity, cardiac fibrotic area, and pulmonary arteriole condition. Lung and serum were under the proteomic analysis. Levels of three identified proteins were measured. Compared with sham and OAMI mice, PH-OAMI mice showed heart dysfunction, low pulmonary blood flow, high right ventricular systolic pressure, heavy heart and lung weight, large cardiac fibrotic area, and pathological pulmonary arteriole remodeling (P<0.05 or P<0.01). Haptoglobin, annexin A5, and Ig mu chain C region of lung and serum were changed significantly in PH-OAMI mice (P<0.01). Then, we collected serum and clinical data, measured three serum protein levels, and performed multivariate regression and receiver operating characteristic curve in patients (normal, OAMI, and PH-OAMI groups). Compared with normal and OAMI patients, serum levels of three proteins in PH-OAMI patients were also altered notably (P<0.01). These three proteins can predict PH in OAMI patients (P<0.01). Receiver operating characteristic curve analysis revealed haptoglobin (cut-off value: 78.295, sensitivity: 62.8%, specificity: 94.4%), annexin A5 (cut-off value: 151.925, sensitivity: 41.9%, specificity: 82.4%), and Ig mu chain C region (cut-off value: 168.885, sensitivity: 86.0%, specificity: 79.6%) (P<0.01). Three circulating serum proteins can be useful for the categorization of OAMI patients with and without PH.