High serum levels of procollagen type III N-terminal amino peptide in patients with congenital heart disease

OBJECTIVE: The serum concentration of aminoterminal procollagen type III (PIIIP) is considered a useful marker of tissue fibrogenesis. The present study tested the hypothesis that: serum PIIIP levels are elevated in patients with congenital heart disease (CHD) and abnormal haemodynamic loading and/or hypoxaemia; PIIIP levels are associated with the severity of haemodynamic load or hypoxaemia, both of which enhance myocardial fibrosis. METHODS AND RESULTS: Serum PIIIP levels were measured in five groups of CHD patients (42 patients with ventricular septal defect (VSD), 26 with coarctation of the aorta (COA, n = 19) or aortic stenosis (AS, n = 7), 36 with atrial septal defect (ASD), 39 with pulmonary stenosis (PS) and 20 with tetralogy of Fallot (TOF)). PIIIP levels of CHD patients were significantly higher than those of 42 control subjects (p<0.05, each). Serum PIIIP levels increased in parallel with increased ventricular volume load in VSD and ASD, and with the severity of PS. In TOF patients, PIIIP levels correlated negatively with arterial oxygen saturation. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) was associated with low levels of PIIIP in COA/AS patients despite the existing haemodynamic load. CONCLUSION: The increased serum PIIIP levels in proportion to the severity of ventricular load or cyanosis suggest enhanced myocardial synthesis of collagen type III in patients with CHD. Suppression of the PIIIP level by ACEI suggests the involvement of the renin-angiotensin-aldosterone system in myocardial fibrosis. These data provide the basis for the development of new diagnostic and therapeutic strategies in patients with CHD.