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Circulating fibrocytes and pulmonary arterial hypertension

To the Editors:

We read with great interest the recent editorial by Stenmark et al. [1] about the potential role of fibrocytes in pulmonary arterial hypertension (PAH) and the original article by Nikam et al. [2] showing the contribution of bone marrow-derived circulating fibrocytes to hypoxic vascular remodelling and inhibition of their recruitment by treprostinil. Many recent reports indicate a contribution of endothelial and haematopoietic progenitor cells [3], attracted via the CXC chemokine ligand 12/CXC chemokine receptor (CXCR)4 axis in the lung [4], but the role of fibrocytes in PAH is still not clear. A previous study of pulmonary hypertension in rat and calf models has shown that pulmonary adventitial remodelling is due to robust recruitment of nonresident, bone marrow-derived cells that can produce collagen and express smooth muscle cell α-actin, thus representing fibrocytes [5]. A unique feature of fibrocytes, described by Bucala et al. [6], is that they circulate in the bloodstream and are capable of producing extracellular matrix components. They express a variety of mesenchymal markers, including collagen-1, collagen-3, vimentin, haematopoietic markers, such as CD11b and CD45, and the stem cell marker CD34 [6]. Circulating fibrocytes display many functional properties, such as phagocytosis, antigen presentation, cytokine and connective tissue matrix production, and the capacity to proliferate and differentiate. In addition, they respond to a variety of cytokines and growth factors. Fibrocytes also produce angiogenic factors, such as vascular endothelial growth factor and platelet-derived growth factor A, and thus have a potent effect on de novo blood vessel formation, as evidenced by studies in an in vivo Matrigel™ (BD Biosciences, Franklin Lakes, NJ, USA) model of angiogenesis. Fibrocyte expression of matrix metalloproteinase-9, which mediates endothelial cell invasion, further facilitates the angiogenic …