The relationship between endothelial progenitor cells and pulmonary arterial hypertension in children with congenital heart disease

Abstract

BackgroundPulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD.MethodsIn this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /μL of peripheral blood was calculated using the following formula: EPCs /μL = WBC /L × lymphocytes % × EPCs % × 10− 6.ResultsThe median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/μL, 1.30 /μL and 0.98/μL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16–0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05).ConclusionThe findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.

Progenitor/Stem Cells in Vascular Remodeling during Pulmonary Arterial Hypertension

“…As mentioned previously, numerous studies have established differences in the number and the phenotype of EPC between PAH and control patients; levels of circulating EC and EPC seem to be elevated in PAH patients, and the number of these cells could be positively correlated with pulmonary artery pressure [18,20,160,161], but other works reported opposite observations [11][12][13][14][15]. Therefore, the relevance of EPC continues to be discussed as a potential biomarker for the PAH, and this is closely related to the choice of markers used to discriminate these endothelial cell populations [162,163] and also to the clinical PH case studied [164,165].…”

“…However, others have shown that an elevated number in human idiopathic PAH and pulmonary fibrosis lung samples could be correlated with the severity of the disease and high pulmonary arterial pressure [17][18][19][20][21]. These results suggested a compensatory EPC proliferation in patients with end-stage PAH [22], and the higher the mPAP is, the more EPCs are consumed to repair pulmonary endothelium, causing a reduction in the number of EPCs [13]. CD133 + or CD133 + /KDR + cells were also found within arterial lesions in PAH patients suggesting that these EPCs may indeed participate in the vascular remodeling process by generating new EC [17,18,21].…”

“…Studies have displayed contrasted results on the regulation of circulating EPC during PAH by measuring blood cells expressing different combinations of the markers CD133, CD34, and VEGFR-2. Circulating EPC were found reduced in some cases inversely correlated with the increase in the mean pulmonary arterial pressure (mPAP) [11][12][13][14][15][16]. However, others have shown that an elevated number in human idiopathic PAH and pulmonary fibrosis lung samples could be correlated with the severity of the disease and high pulmonary arterial pressure [17][18][19][20][21].…”

Pharmacology of Pulmonary Arterial Hypertension: An Overview of Current and Emerging Therapies

“…Cardiac and vascular stem cells have been suggested before to be potential new therapies for cardiovascular regeneration. , Some investigations in the field of PAH have also shown potentially positive results of stem cell-based therapy with endothelial progenitor cells (EPCs)able to partially rescue endothelial functionand cardiosphere-derived cells (CDCs), which have demonstrated to ameliorate both vascular and ventricular remodelling and no adverse effects were reported. − In addition to these cell types, some other cell types have been explored in stem cell therapy animal models of PAHfew of them directly targeting the RV for RV failure prevention–with modest but promising results …”

The Organ Trail: A Review of Biomarkers of Organ Failure

“…In a pediatric study, EPCs were reported to be highly correlated with pulmonary arterial hypertension in pediatric patients with congenital heart disease ( 54 ). EPCs have also been reported to stratify risk in adult patients with chronic kidney disease (CKD),however the same did not hold true for pediatric patients with predialysis CKD ( 55 ).…”