| Full text | |
| Author(s): |
Maeda, Nair Y.
;
Aiello, Vera D.
;
Santos, Paulo C.
;
Thomaz, Ana M.
;
Kajita, Luiz J.
;
Bydlowski, Sergio P.
;
Lopes, Antonio Augusto
Total Authors: 7
|
| Document type: | Journal article |
| Source: | Mediators of Inflammation; v. 2019, p. 10-pg., 2019-01-01. |
| Abstract | |
Macrophage migration inhibitory factor (MIF) plays an important pathophysiological role in pulmonary hypertension (PHT). Previously, we demonstrated that serum MIF is increased in pediatric PHT associated with congenital heart disease (CHD). In the present study, we determined possible associations between MIF levels, hemodynamic and histological parameters, and mitochondrial carbamyl-phosphate synthetase I (CPSI) T1405N polymorphism in a similar population. The asparagine 1405 variant (related to A alleles in the C-to-A transversion) has been shown to be advantageous in pediatric PHT compared to the threonine 1405 variant (C alleles). Forty-one patients were enrolled (aged 2-36 months) and subsequently divided into 2 groups after diagnostic evaluation: the high-pulmonary blood flow (high PBF) group (pulmonary-to-systemic blood flow ratio 2.58 (2.21-3.01), geometric mean with 95% CI) and the high-pulmonary vascular resistance (high PVR) group (pulmonary vascular resistance 6.12 (4.78-7.89) Wood unitsxm2). Serum MIF was measured using a chemiluminescence assay. The CPSI polymorphism was analyzed by polymerase chain reaction followed by high-resolution melting analysis. Medial hypertrophy of pulmonary arteries was assessed by the histological examination of biopsy specimens. Serum MIF was elevated in patients compared to controls (p=0.045), particularly in the high-PVR group (n=16) (p=0.022) and in subjects with the AC CPSI T1405N genotype (n=16) compared to those with the CC genotype (n=25) (p=0.017). Patients with high-PVR/AC-genotype profile (n=9) had the highest MIF levels (p=0.030 compared with the high-PBF/CC-genotype subgroup, n=18). In high-PVR/AC-genotype patients, the medial wall thickness of intra-acinar pulmonary arteries was directly related to MIF levels (p=0.033). There were no patients with the relatively rare AA genotype in the study population. Thus, in the advantageous scenario of the asparagine 1405 variant (AC heterozygosity in this study), heightened pulmonary vascular resistance in CHD-PHT is associated with medial hypertrophy of pulmonary arteries where MIF chemokine very likely plays a biological role. (AU) | |
| FAPESP's process: | 11/09341-0 - Combined clinical and surgical approaches to congenital heart disease associated with pulmonary arterial hypertension - possible role of genetic and inflammatory markers |
| Grantee: | Antonio Augusto Barbosa Lopes |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/21587-5 - Effects of proinflammatory response on global postoperative cardiopulmonary function in young pediatric patients with congenital cardiac septal defects undergoing surgical treatment: a morbimortality study on different risk groups |
| Grantee: | Antonio Augusto Barbosa Lopes |
| Support Opportunities: | Regular Research Grants |