Schistosomiasis-Induced Experimental Pulmonary Hypertension

Graham, Brian B.; Mentink‐Kane, Margaret M.; El-Haddad, Hazim; Purnell, Shawn M.; Zhang, Li; Zaiman, Ari; Redente, Elizabeth F.; Riches, David W. H.; Hassoun, Paul M.; Bandeira, Angela; Champion, Hunter C.; Butrous, Ghazwan; Wynn, Thomas A.; Tuder, Rubin M.

doi:10.2353/ajpath.2010.100063

Cited by 93 publications

(87 citation statements)

References 50 publications

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“…The infection was done by placing the mice's tails in a vial containing 30-35 cercariae for 30 minutes. 132 Fifty-five days later, mice were challenged intravenously by injection of 5,000 viable eggs (suspended in 0.5 mL of sterile saline) into the tail vein. This intravenous challenge mimicked the deposition of eggs in the lung by collateral shunts, which normally form in chronically infected mice.…”

Section: Chp Combined With Su-5416mentioning

confidence: 99%

A Comprehensive Review: The Evolution of Animal Models in Pulmonary Hypertension Research; Are We there Yet?

et al. 2013

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Pulmonary hypertension (PH) is a disorder that develops as a result of remodeling of the pulmonary vasculature and is characterized by narrowing/obliteration of small pulmonary arteries, leading to increased mean pulmonary artery pressure and pulmonary vascular resistance. Subsequently, PH increases the right ventricular afterload, which leads to right ventricular hypertrophy and eventually right ventricular failure. The pathophysiology of PH is not fully elucidated, and current treatments have only a modest impact on patient survival and quality of life. Thus, there is an urgent need for improved treatments or a cure. The use of animal models has contributed extensively to the current understanding of PH pathophysiology and the investigation of experimental treatments. However, PH in current animal models may not fully represent current clinical observations. For example, PH in animal models appears to be curable with many therapeutic interventions, and the severity of PH in animal models is also believed to correlate poorly with that observed in humans. In this review, we discuss a variety of animal models in PH research, some of their contributions to the field, their shortcomings, and how these have been addressed. We highlight the fact that the constant development and evolution of animal models will help us to more closely model the severity and heterogeneity of PH observed in humans.

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Section: Chp Combined With Su-5416mentioning

confidence: 99%

A Comprehensive Review: The Evolution of Animal Models in Pulmonary Hypertension Research; Are We there Yet?

et al. 2013

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“…Perivascular infi ltration of infl ammatory cells around remodeled vessels has consistently been demonstrated in animal models of PAH, including the mouse model of Sch-PAH and in patients with IPAH [ 43 ]. The cells involved are T-cells, macrophages, B cells, mast cells, and dendritic cells in the adventitia and media of muscular pulmonary arteries.…”

Section: Pathogenesismentioning

confidence: 95%

“…The injection of eggs alone was not suffi cient to cause right ventricular hypertension, so the embolic disease alone does not seem to cause experimental PAH [ 43 ]. Studies with lung samples collected at autopsies of individuals with Sch-PH demonstrated pulmonary vascular remodeling with plexiform lesions and arterial medial thickening in all 18 samples examined, but failed to fi nd eggs of the parasite.…”

Section: Pathogenesismentioning

confidence: 98%

“…The authors suggested that the enhanced lung infl ammatory response triggered by the challenge with eggs correlates with the development of experimental Sch-PAH. The granulomas formed are composed of macrophages, eosinophils, and cells containing smooth muscle actin, which could represent myofi broblasts and/or differentiated smooth muscle cells [ 43 ]. Crosby et al [ 45 ] demonstrated that IL-13 but not IL-4 stimulated the migration of pulmonary artery smooth muscle cells in transwell assays.…”

Section: Pathogenesismentioning

confidence: 99%

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Schistosomiasis-Associated Pulmonary Arterial Hypertension

Ferreira

Bandeira

Domingues

2015

Diagnosis and Management of Pulmonary Hypertension

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Schistosomiasis is the third most common endemic disease and has been considered the most common cause of pulmonary arterial hypertension (PAH) in the world. Around 6 % of people with chronic schistosomiasis in endemic areas are affected. Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is classifi ed by the World Health Organization as group 1 pulmonary arterial hypertension because it has clinical, pathological, and hemodynamic characteristic that are similar to idiopathic pulmonary arterial hypertension. Sch-PAH is a severe disease that affects mainly middle-aged women. Symptoms and signs of right-heart insuffi ciency may be present, such as dyspnea, syncope, and peripheral edema. It has been demonstrated that Sch-PAH has a more benign clinical course and a better survival than idiopathic pulmonary hypertension. There are few reports of any benefi cial effect from specifi c therapy directed toward group 1 PAH in this population of patients. The mechanisms responsible for the development of pulmonary hypertension in patients with schistosomiasis are unknown. There is growing evidence that vessel obstruction and granulomatous reaction to pulmonary embolization of eggs is not the sole mechanism that causes the disease. Further studies are needed to better elucidate the pathogenesis of Sch-PAH and to develop targeted therapies for this devastating disease.

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“…Observations suggest that chronic HIV-associated inflammation leads to an accumulation of asymmetrical dimethylarginine, which is a well-known endogenous inhibitor of endothelial nitric oxide synthase, and, thus, promotes endothelial dysfunction and vascular smooth muscle cell proliferation. [63][64][65] Additionally, Nef and Tat proteins modulate the release of IL-2 and monocyte chemotactic protein-1 (MCP-1, also known as CCL2), which stimulate pulmonary vascular remodeling, 66,67 particularly in Schistosomiasis infection 68,69 ( Figure 2). Whether overlap in cytokine activation patterns in Schistosomiasis and HIV is responsible for PAH in coinfected patients, however, requires further investigation.…”

Section: Contemporary Hypothesesmentioning

confidence: 99%