Inflammation in pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study.
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France; Department of Pulmonary Hypertension, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, England.
Laura C
LC
Price
Department of Pulmonary Hypertension, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, England.
S John
SJ
Wort
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Frédéric
F
Perros
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Peter
P
Dorfmüller
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Alice
A
Huertas
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
David
D
Montani
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France.
Sylvia
S
Cohen-Kaminsky
Faculté de Médecine, Université Paris-Sud, Kremlin Bicêtre, France; Service de Pneumologie et Réanimation Respiratoire, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique, Hôpitaux de Paris, Clamart, France; INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France. Electronic address: marc.humbert@abc.aphp.fr.
Marc
M
Humbert
D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
D016207:Cytokines