Apelin: A new plasma marker of cardiopulmonary disease
Introduction
Dyspnea is a major symptom of both parenchymal lung disease and congestive heart failure. Examination of patients with dyspnea therefore includes evaluation of pulmonary as well as cardiac function by chest X-ray, microbiological screening, measurement of the ventilatory status, and echocardiographic assessment of cardiac function. Measurement of the cardiac-derived B-type natriuretic peptide (BNP) or its precursor (proBNP) has been used as markers of cardiovascular causes of dyspnea, where increased plasma concentrations are associated with congestive heart failure, pulmonary embolism, or pulmonary vascular disease [1]. In contrast, plasma BNP and proBNP concentrations seem to be unaffected in patients with strictly parenchymal lung disease [2]. Until now, however, there have been no specific endocrine markers to assess the lung parenchyma.
Apelin is a novel peptide identified as the endogenous ligand to the APJ (angiotensin receptor-like 1) receptor [3]. Although apelin initially was identified in cow stomach, both apelin and the APJ receptor are expressed in cardiac tissue [4], [5]. Recent reports have furthermore established that apelin exerts a positive inotropic effect on both normal hearts and in heart failure after myocardial infarction [4], [6]. While this inotropic effect suggests an important biological role in endocrine regulation of heart function, the potential clinical use of apelin measurement in human plasma is still unknown, as few studies have reported both increased and decreased concentrations in heart failure patients [5], [7]. Interestingly, apelin mRNA and peptide are predominantly expressed in normal mammary and lung tissue from rat [8]. We therefore hypothesized that apelin concentrations in plasma may be affected in patients with chronic parenchymal lung disease without cardiac dysfunction.
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Patients
Venous plasma was obtained from patients with chronic parenchymal lung disease (chronic obstructive pulmonary disease, fibrosis, or emphysema, n = 53) or idiopathic pulmonary hypertension (n = 10) referred for evaluation prior to lung transplantation. Notably, patients considered clinically unfit for transplantation were not included. Left and right heart catheterization was performed and the hemodynamic status was determined. Inclusion criteria were normal left ventricular systolic function on
Results
The patient characteristics including hemodynamic findings from the invasive examination are shown in Table 1. Ventilatory examination further corroborated the severely reduced respiratory function in the chronic parenchymal lung disease patients (median forced expiratory volume (FEV1): 29% of expected (range 16–73%), forced ventilatory capacity (FVC): 57% of expected (26–103%), and pulmonary diffusing capacity: 34% of expected (7–90%). Of note, cardiac function determined as left ventricular
Discussion
This is the first report demonstrating decreased plasma concentrations of apelin-36 in patients with chronic parenchymal lung disease and preserved LVEF. Accordingly, plasma measurement of apelin-36 may provide diagnostic information in patients with severe pulmonary disease. The present results also corroborate a previous observation of reduced plasma apelin-36 concentrations in chronic heart failure patients [7]. As plasma concentrations of BNP and its precursor, proBNP, are increased in
Acknowledgments
The skilful technical assistance of Lone Olsen and Bo Lindberg is gratefully acknowledged.
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