The inter-connection between fibrosis and microvascular remodeling in idiopathic pulmonary fibrosis: Reality or just a phenomenon

Abstract

BackgroundIdiopathic pulmonary fibrosis is the most frequent interstitial disease with the worst prognosis. It is characterized by an uncontrolled fibrosis which is difficult to manage. The pathogenesis of this disease remains unclear with many theories resulting in multiple target therapies. The relation between fibrosis and vascular remodeling has been debated in the literature with different results that may seem contradictory.AimWe target to evaluate the connection between fibrosis and vascular remodeling in usual interstitial pneumonia.Material and methods26 cases of idiopathic pulmonary fibrosis were reviewed by 2 pathologists and the diagnosis of UIP was retained according to the American Thoracic Society's criteria. Fibrotic changes and vascular remodeling were evaluated blindly. The fibrotic changes were classified as severe, intermediate and mild. Vascular occlusion was graded in 4 grades extending from medial hypertrophy (grade 1) to plexiform lesions of the vascular wall (grade 4).ResultsWe noticed that severe degrees of fibrosis were correlated with severe grades of vascular obstruction. In fact, our 26 cases were classified as severe fibrosis in 11 cases with grade IV vascular lesions in 6 cases, intermediate fibrosis in 12 cases with grade II vascular lesions in 8 cases and mild fibrosis in 3 cases with grade I vascular lesions in all cases.ConclusionMany theories have been reported concerning the UIP's pathogenesis. Recently, many authors reported that the primum movens of these lesions was an epithelial/endothelial injury which induces uncontrolled fibrosis and microvascular remodeling using different pathways. This puts emphasis on the necessity of multi-target therapies in order to improve the management of this fatal disease.

Histological hallmarks and role of Slug/ PIP axis in pulmonary hypertension secondary to pulmonary fibrosis

“…In the present study, we showed a correlation between fibrosis severity and vascular wall thickness in end‐stage PF‐PH patients (Fig F and G). This correlation was previously described in PF patients (Parra et al , ; Mlika et al , ) and agrees with the data presented here. The presence of vascular remodeling in the non‐fibrotic areas of the lung in PF‐PH patients was suggested by others, yet never previously quantified (Heath et al , ; Kim et al , ).…”

“…PF‐PH has been viewed as a process driven by lung fibrosis. This view is supported by the study from Colombat et al () who found a significant positive correlation between the macroscopic extent of lung fibrosis and mean pulmonary artery pressure in idiopathic PF patients, and by other studies reporting a correlation between vascular wall thickness and severity of lung fibrosis in PF (Parra et al , ; Mlika et al , ). However, other clinical reports did not find any correlation between increased mPAP and lung fibrosis (Mura et al , ) as measured by high‐resolution chest CT or forced vital capacity of PF patients (Nadrous et al , ; Zisman et al , ; Nathan et al , ).…”

Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series)

“…Increases in the bronchial vasculature are noted in bleomycin‐induced PF in mice 24 . Despite these findings, most studies have concentrated on alveolar capillaries because the alveolar parenchyma is the region most affected by fibrotic remodeling in this disease 25 – 27 . This review will largely focus on factors affecting the alveolar microvasculature 28 since alterations in this region have a well‐established role in the pathogenesis of both PF and emphysema.…”

Vascular dysfunction in aged mice contributes to persistent lung fibrosis

“…Aberrant vascular remodeling is a previously noted feature in the pathogenesis of IPF, and increased capillary irregularities including vessel dilatation and loss of microvasculature have been observed in IPF lungs (Barratt & Millar, 2014; Mlika, Bacha, Braham, & El Mezni, 2016; Renzoni, 2004). Although these vascular abnormalities have been well documented, whether they are important drivers of disease progression still remains debated.…”