Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension

Abstract

Pulmonary hypertension is characterised by a progressive increase in pulmonary arterial resistance due to endothelial and smooth muscle cell proliferation resulting in chronic obstruction of small pulmonary arteries. There is evidence that inflammatory mechanisms may contribute to the pathogenesis of human and experimental pulmonary hypertension.The aim of the study was to address the role of fractalkine (CX3CL1) in the inflammatory responses and pulmonary vascular remodelling of a monocrotaline-induced pulmonary hypertension model.The expression of CX3CL1 and its receptor CX3CR1 was studied in monocrotaline-induced pulmonary hypertension by means of immunohistochemistry and quantitative reverse-transcription PCR on laser-captured microdissected pulmonary arteries.It was demonstrated that CX3CL1 was expressed by inflammatory cells surrounding pulmonary arterial lesions and that smooth muscle cells from these vessels had increased CX3CR1 expression. It was then shown that cultured rat pulmonary artery smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but not migration of these cells.In conclusion, the current authors proposed that fractalkine may act as a growth factor for pulmonary artery smooth muscle cells. Chemokines may thus play a role in pulmonary artery remodelling.

Pulmonary vascular dysfunction in end-stage cystic fibrosis: role of NF- B and endothelin-1

“…Although hypoxaemia is usually present in these patients and undoubtedly partly underlies the increase in pulmonary vascular resistance, other mechanisms are likely to be involved. To date, they have been poorly elucidated, maybe due to the fact that very few studies have focused on the pulmonary vascular tone and remodelling in humans affected by chronic lung diseases, in contrast to idiopathic PH [3][4][5]. In order to get some insights into the mechanisms underlying the pulmonary vascular impact of chronic obstructive lung diseases, we set up a study in one of them: cystic fibrosis (CF).…”

Corticoide sistêmico como tratamento de primeira linha da hipertensão pulmonar secundária a síndrome POEMS

“…Patients with POEMS syndrome markedly show high levels of serum cytokines, particularly TNF-α, IL-6, IL-1β and vascular endothelial growth factor (VEGF). (4,6,7) More recently, one group of authors reported a case in which VEGF was determined before and after the initiation of corticosteroid treatment and noted that the serum levels of this cytokine decreased significantly. (5) The expression of VEGF is intimately related to the formation of plexiform vascular lesions in the lungs of patients with severe idiopathic pulmonary arterial hypertension and in those patients with pulmonary arterial hypertension of other causes.…”

“…(1,2) The co-occurrence of these two clinical conditions might be linked to increased levels of proinflammatory cytokines. (3)(4)(5)(6)(7) The potential relation between the inflammatory process and the development and modulation of pulmonary hypertension (8) is confirmed by a significant response to immunosuppressants when the clinical condition associated with the development of pulmonary hypertension is predominantly inflammatory, e.g., systemic lupus erythematosus and mixed connective tissue disease. (9) Such findings provide the theoretical basis for the use of immunosuppressive therapy in pulmonary hypertension accompanied by POEMS syndrome.…”

Small airway obstruction in severe pulmonary arterial hypertension correlates with increased airway CD8+ T-cells and fractalkine expression

“…Although we can not formally exclude a difference in sensitivity of CD8 versus CD4 tissue immunodetection, T-cell infiltrates seem to predominantly consist of CD8+ lymphocytes. It is tempting to speculate that fractalkine, which appears to be increased within epithelial and subepithelial areas of the airways in our severe PAH patients, could trigger smooth muscle hypertrophy [7] around the airways that could account for peripheral airway obstruction and hyperresponsiveness. Airway infiltration by CD8+ T-cells has been observed in chronic obstructive pulmonary disease (COPD) c EUROPEAN RESPIRATORY JOURNAL VOLUME 34 NUMBER 6 [8], as well as in severe asthma [9] and has been related to lung function decline.…”