Serum Levels of Soluble ICAM-1 in Children with Pulmonary Artery Hypertension

Abstract

This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings.Our C ongenital heart disease (CHD) is the most common congenital malformation: the prevalence of moderate and severe forms of CHD is about 6 in 1,000 live births, or 19 in 1,000 live births if potentially serious cases of bicuspid aortic valve are included.1 Pulmonary artery hypertension (PAH) is a frequent complication of CHD, particularly in patients who have left-to-right shunts.2 Pulmonary artery hypertension has been defined as an increase in mean pulmonary artery pressure (PAP) of ≥25 mmHg at rest, as evaluated by right-sided heart catheterization. 3Pulmonary artery hypertension has a multifactorial pathogenesis that involves various biochemical pathways and cell types. The increase in pulmonary vascular resistance is related to different mechanisms, including vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall, inflammation, and thrombosis. Persistent exposure of the pulmonary vasculature to increased blood flow and pressure can result in endothelial dysfunction and endothelial damage.2 After such damage, endothelial cells produce an array of cytokines and growth factors and promote immune cells to adhere to and migrate through the vessel wall into the extravascular space. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are expressed on endothelial cells. When overexpressed on the activated endothelial layer, VCAM-1 and ICAM-1 undergo shedding, and their soluble forms (detectable in serum) are considered to be markers of endothelial cell activity or injury. 5,6 In the medical literature, 7-9 elevated serum concentrations of adhesion molecules have been detected in several diseases, such as diabetes mellitus, coronary heart disease, atherosclerosis, and rheumatoid arthritis. Sungprem and colleagues 10 showed that serum ICAM-1 level was increased in patients with PAH.

Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover Conference Series)

“… 144 Likewise, soluble intercellular adhesion molecule-1 (ICAM-1) levels in serum are significantly higher in children with PAH secondary to CHD compared to children with CHD without associated PAH, or in a healthy control group. 145 , 146 ICAM-1 levels are also increased in iPAH patients and patients with PAH associated with connective tissue disease (PAH-CTD), whereas circulating levels of soluble vascular cell adhesion protein 1 (VCAM-1) were elevated in PAH-CTD only. 147 Conversely, soluble ICAM-1 levels decreased when young patients with CHD and PH were treated with the phosphodiesterase 5 inhibitor sildenafil.…”

Functional State of Vascular Endothelium in Patients With Pulmonary Arterial Hypertension Associated With Congenital Heart Diseases

“…Исследования процессов ремоделирования сосудов МКК у больных ЛАГ на фоне ВПС установили, что пролиферация гладких мышечных и эндотелиальных клеток является ведущим механизмом увеличения сосудистого сопротивления в русле МКК [4][5][6]. У пациентов с левоправыми шунтами на фоне ВПС, т. е. вследствие прекапиллярной ЛАГ, нарушение баланса регуляторных факторов (оксида азота, простациклина и брадикинина с одной стороны, эндотелина-1 и ангиотензина II, с другой) и последующее изменение структуры сосудистой стенки происходят в результате увеличения напряжения сдвига эндотелиоцитов под влиянием гемодинамической перегрузки МКК [7][8][9].…”

Emerging Biomarkers of Congenital Heart Diseases and Disorders

“…It is used to identify mothers at higher risk to deliver affected children. ICAM-1 is a potential biomarker to be used for the diagnosis and follow-up of pulmonary artery hypertension (Table 2) [36]. Other important immunological biomarkers which could provide better specificity about CHD are levels of different cytokines, chemokines, circulating antigens, antibodies in serum and constitutively expressed natural auto antibodies (na-Ab) which interact specifically with different self-antigens and plurality of anti-self receptors of auto reactive T-lymphocytes.…”

“…Serum levels of soluble ICAM-1 can provide confirmation about pulmonary artery hypertension in children [36]. Similarly, total right/left-volume index should be used as a new and simplified CMR measure, allowing more accurate assessment of disease severity [44].…”