Inflammation in Pulmonary Arterial Hypertension

Abstract

Inflammation in pulmonary arterial hypertension. P. Dorfmüller, F. Perros, K. Balabanian, M. Humbert. #ERS Journals Ltd 2003. ABSTRACT: Inflammatory mechanisms appear to play a significant role in some types of pulmonary hypertension (PH), including monocrotaline-induced PH in rats and pulmonary arterial hypertension of various origins in humans, such as connective tissue diseases (scleroderma, systemic lupus erythematosus, mixed connective disease), human immunodeficiency virus infection, or plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal (M) protein and skin changes (POEMS) syndrome.Interestingly, some patients with severe pulmonary arterial hypertension associated with systemic lupus erythematosus have experienced significant improvements with immunosuppressive therapy, emphasising the relevance of inflammation in a subset of patients presenting with PH. Patients with primary PH (PPH) also have some immunological disturbances, suggesting a possible role for inflammation in the pathophysiology of this disease. A subset of PPH patients have been shown to have circulating autoantibodies, including antinuclear antibodies, as well as elevated circulating levels of the pro-infammatory cytokines, interleukins -1 and -6. Lung histology has also revealed inflammatory infiltrates in the range of plexiform lesions in patients displaying severe PPH, as well as an increased expression of the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES) and fractalkine.Further analysis of the role of inflammatory mechanisms is necessary to understand whether this component of the disease is relevant to its pathophysiology. Pulmonary arterial hypertension (PAH) is characterised by an elevated mean pulmonary artery pressure o25 mmHg at rest, with a normal pulmonary artery wedge pressure. This severe condition leads to progressive right heart failure and ultimately death [1]. The Evian Classification reflects recent advances in the understanding of pulmonary hypertensive diseases, and recognises the similarity between "unexplained" pulmonary hypertension (PH) (primary PH (PPH)) and PAH of certain known aetiologies, such as collagen vascular diseases, human immunodeficiency virus (HIV) infection, portal hypertension, congenital systemic-to-pulmonary shunts and anorexigen exposure [2].PAH results from chronic obstruction of small pulmonary arteries, which is due, at least in part, to endothelial and vascular smooth muscle cell dysfunction and proliferation [3]. The recent discovery that a significant proportion of patients with familial, as well as sporadic, PPH have germline mutations of genes encoding receptor members of the transforming growth factor (TGF)-b family (bone morphogenetic protein receptor-II and activin receptor-like kinase-1), suggests that dysfunctional TGF-b signalling could lead to an abnormal proliferation of pulmonary vascular cells [4,5]. Although these major advances have improved the understanding of PAH, more information is needed to evaluate th...

Enhanced Pulmonary Arteriopathy in Simian Immunodeficiency Virus–infected Macaques Exposed to Morphine

“…Inflammation plays a key role in the development of many forms of pulmonary arterial diseases and resultant pulmonary arterial hypertension (21)(22)(23). Morris and colleagues recently reported for the first time a link between echocardiographic manifestations related to pulmonary vascular disease and the inflammatory phenotype in HIV-infected individuals (49).…”

Clinical features of pulmonary arterial hypertension in patients receiving dasatinib

“…Typical PAH is progressive, persistent, and has a poor prognosis without intervention as the progressive increase in pulmonary vascular resistance can eventually cause right ventricular (RV) Figure 1. Mechanisms of PAH, based on previously published research in human subjects [12,16,17]. Many molecules and signaling pathways have been implicated in the pathobiological mechanisms identified in the cells and tissues of patients with PAH.…”

“…PAH is defined by a number of pathophysiological changes in the pulmonary arteries ( Fig. 1) that contribute to increased pulmonary vascular tone, pulmonary vascular remodeling, and RV hypertrophy/overload [12][13][14][16][17][18]. Various molecules and signaling pathways implicated in pathobiological mechanisms for PAH have been identified (Fig.…”

Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-κB pathway inhibition: Contribution of chlorogenic acid

“…Inflammation is pointed out in preclinical studies as a major mechanism in the pathogenesis of chronic diseases, namely diabetes, hypertension and cancer (Liu and Zeng, 2012;Osborn and Olefsky, 2012;Price et al, 2012). During an inflammatory response, macrophages release several inflammatory mediators, such as cytokines, which expression is regulated by different intracellular signaling pathways (O'Neill, 2006).…”