Recruitment and involvement of bone/blood-derived circulating fibrocytes (CF) in the promotion of fibrotic tissue remodelling processes have shown by several reports. However, their direct contribution to pathological changes is not clear. The purpose of the present investigation is to delineate the causal role of circulating fibrocytes in the pathogenesis of pulmonary hypertension (PH).
For selective ablation of CF, we applied the suicidal gene strategy with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir. The transgenic mice were generated, having HSV-TK-GFP transgene under the collagen1 promoter. To selectively target CF, HSV-TK-GFP+ bone marrow from transgenic mice transplanted into irradiated wild type mice. These chimera mice subjected to hypoxia for PH induction and ganciclovir treatment for CF ablation.
In vivo circulating fibrocytes ablation reduced right ventricular hypertrophy, vascular remodelling with reduced total collagen content. We quantified the CF recruited in the perivascular area and arterial wall of small pulmonary arteries. There was significant recruitment of circulating fibrocytes in the lung in response to hypoxia. The characterization of CF showed the expression of CD45, collagen1 (GFP) along with alpha-smooth muscle actin (╬▒SMA).
Our data demonstrate that circulating fibrocytes ablation has a potential impact on right ventricular hypertrophy and vascular remodelling in the setting of experimental PH induced by hypoxia. The beneficial effects may be related to the direct contribution of fibrocytes or its paracrine effect on other resident cell types. Thus, clinical manipulation of circulating fibrocytes may represent a novel therapeutic approach to ameliorate disease state in PH.

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