Faculty Opinions recommendation of Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension.

2013 ◽  
Author(s):  
Vinicio de Jesus Perez
Keyword(s):  
Pulmonary Hypertension ◽  
Leukotriene B4 ◽  
Endothelial Injury

scholarly journals Blocking Macrophage Leukotriene B4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension

2013 ◽  
Vol 5 (200) ◽  
pp. 200ra117-200ra117 ◽  
Author(s):  
W. Tian ◽  
X. Jiang ◽  
R. Tamosiuniene ◽  
Y. K. Sung ◽  
J. Qian ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Leukotriene B4 ◽  
Endothelial Injury

scholarly journals Regulatory T Cells Limit Vascular Endothelial Injury and Prevent Pulmonary Hypertension

2011 ◽  
Vol 109 (8) ◽  
pp. 867-879 ◽  
Author(s):  
Rasa Tamosiuniene ◽  
Wen Tian ◽  
Gundeep Dhillon ◽  
Lijuan Wang ◽  
Yon K. Sung ◽  
...  
Keyword(s):  
T Cells ◽  
Pulmonary Hypertension ◽  
Regulatory T Cells ◽  
Endothelial Injury ◽  
Vascular Endothelial

Suppression of Intimal Hyperplasia by a 5-lipoxygenase Inhibitor, MK-886: Studies with a Photochemical Model of Endothelial Injury

1998 ◽  
Vol 79 (03) ◽  
pp. 635-639 ◽  
Author(s):  
Kazuo Umemura ◽  
Tomohiro Ohmura ◽  
Hisakuni Hashimoto ◽  
Mitsuyoshi Nakashima ◽  
Kazunao Kondo
Keyword(s):  
Receptor Antagonist ◽  
Green Light ◽  
Major Complication ◽  
Percutaneous Transluminal Coronary Angioplasty ◽  
Leukotriene B4 ◽  
Endothelial Injury ◽  
Intimal Thickening ◽  
Lipoxygenase Inhibitor ◽  
Transluminal Coronary Angioplasty ◽  
Percutaneous Transluminal

SummaryIntimal thickening is a major complication following percutaneous transluminal coronary angioplasty, which leads to restenosis and requires reoperation. We have investigated the effect of a 5-lipoxygenase inhibitor, MK-886, a leukotriene B4 (LTB4) receptor antagonist, ONO-4057 or a LTC4 and LTD4 receptor antagonist, ONO-1078, on intimal thickening. Photochemical reaction between green light and systemically administered Rose Bengal produced intimal thickening in the rat femoral artery. Each drug was administered orally, once a day for 7 days, starting just after the endothelial injury. Both MK-886 administration, 10 mg/kg, and ONO-4057 administration, 100 mg/kg, suppressed intimal thickening level examined three weeks after endothelial injury, while similarly administered ONO-1078 did not. In cultured rat-derived smooth muscle cells, LTB4, an active metabolite of 5-lipoxygenase whose biosynthesis in air pouch exudate was suppressed by MK-886, stimulated cell migration. Based on these observations, the 5-lipoxygenase may have a key role in intimal thickening via its metabolites such as LTB4.

scholarly journals Leukotriene B4 mediates macrophage influx and pulmonary hypertension in bleomycin-induced chronic neonatal lung injury

2016 ◽  
Vol 311 (2) ◽  
pp. L292-L302 ◽  
Author(s):  
Mong Tieng Ee ◽  
Crystal Kantores ◽  
Julijana Ivanovska ◽  
Mathew J. Wong ◽  
Amish Jain ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Cell Types ◽  
Leukotriene B4 ◽  
Experimental Models ◽  
Neonatal Rat ◽  
Lipoxygenase Inhibitor ◽  
Human Infants ◽  
Rat Pups ◽  
Factor Α

Systemically-administered bleomycin causes inflammation, arrested lung growth, and pulmonary hypertension (PHT) in the neonatal rat, similar to human infants with severe bronchopulmonary dysplasia (BPD). Leukotrienes (LTs) are inflammatory lipid mediators produced by multiple cell types in the lung. The major LTs, LTB4 and cysteinyl LTs, are suggested to contribute to BPD, but their specific roles remain largely unexplored in experimental models. We hypothesized that LTs are increased in bleomycin-induced BPD-like injury, and that inhibition of LT production would prevent inflammatory cell influx and thereby ameliorate lung injury. Rat pups were exposed to bleomycin (1 mg·kg−1·day−1 ip) or vehicle (control) from postnatal days 1–14 and were treated with either zileuton (5-lipoxygenase inhibitor), montelukast (cysteinyl LT1 receptor antagonist), or SC57461A (LTA4 hydrolase inhibitor) 10 mg·kg−1·day−1 ip. Bleomycin led to increased lung content of LTB4, but not cysteinyl LTs. Bleomycin-induced increases in tissue neutrophils and macrophages and lung contents of LTB4 and tumor necrosis factor-α were all prevented by treatment with zileuton. Treatment with zileuton or SC57461A also prevented the hemodynamic and structural markers of chronic PHT, including raised pulmonary vascular resistance, increased Fulton index, and arterial wall remodeling. However, neither treatment prevented impaired alveolarization or vascular hypoplasia secondary to bleomycin. Treatment with montelukast had no effect on macrophage influx, PHT, or on abnormal lung structure. We conclude that LTB4 plays a crucial role in lung inflammation and PHT in experimental BPD. Agents targeting LTB4 or LTB4-mediated signaling may have utility in infants at risk of developing BPD-associated PHT.

scholarly journals Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice

2008 ◽  
Vol 295 (2) ◽  
pp. H677-H690 ◽  
Author(s):  
Yanli Song ◽  
Laura Coleman ◽  
Jianru Shi ◽  
Hideyuki Beppu ◽  
Kaori Sato ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Transforming Growth Factor ◽  
Systolic Pressure ◽  
Receptor Expression ◽  
Endothelial Injury ◽  
Persistent Pulmonary Hypertension ◽  
Pcr Analysis ◽  
Type I ◽  
Wild Type ◽  
Bmp Receptors

Heterozygous bone morphogenetic protein receptor-II-knockout (BMPR2+/−) mice have a similar genetic trait like that in some idiopathic pulmonary arterial hypertension patients. To examine the effect of pulmonary endothelial injury in BMPR2+/− mice, we challenged the mice with two injections of monocrotaline combined with intratracheal instillation of replication-deficient adenovirus expressing 5-lipoxygenase (MCT+Ad5LO). After the challenge (1 wk), BMPR2+/− mice exhibited a doubling of right ventricular systolic pressure that was greater than that of wild-type mice and remained elevated for 3 wk before heart failure developed. Muscularization and thickening of small pulmonary arterioles was evident in the BMPR2+/− lungs at 2 wk after the challenge and became severe at 3 wk. Marked perivascular infiltration of T cells, B cells, and macrophages was associated with the remodeled vessels. Real-time PCR analysis showed that the expression of six endothelial cell markers in lung tissue was decreased to 20–40% of original levels at 1 wk after the challenge in both BMPR2+/− and wild-type mice and largely recovered in wild-type (50–80%) but not BMPR2+/− lungs (30–50%) at 3 wk after the challenge. Macrophage inflammatory protein-1α and fractalkine receptor expression doubled in BMPR2+/− compared with wild-type lungs. Expression of type I and type II BMP receptors, but not transforming growth factor-β receptors, in the challenged BMPR2+/− and wild-type lungs showed a similar pattern of expression as that of endothelial markers. Apoptotic responses at 1 wk after MCT and Ad5LO challenge were also significantly greater in the BMPR2+/− lungs than the wild-type lungs. These data show that BMPR2+/− mice are more sensitive to MCT+Ad5LO-induced pulmonary hypertension than wild-type mice. Greater endothelial injury and an enhanced inflammatory response could be the underlying causes of the sensitivity and may work in concert with BMPR2 heterozygosity to promote the development of persistent pulmonary hypertension.

scholarly journals Pulmonary Hypertension in COVID-19 Pneumoniae: It Is Not Always as It Seems

2020 ◽  
Author(s):  
Maria Cristina Pasqualetto ◽  
Maria Domenica Sorbo ◽  
Maria Vitiello ◽  
Chiara Ferrara ◽  
Moreno Scevola ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Pulmonary Hypertension ◽  
Viral Infection ◽  
Right Ventricular ◽  
Pulmonary Circulation ◽  
Venous Drainage ◽  
Endothelial Injury ◽  
Positive End Expiratory Pressure ◽  
Hypoxic Vasoconstriction ◽  
Pulmonary Haemodynamics

A patient affected by COVID-19 pneumonia may develop pulmonary hypertension (PH) and secondary right ventricular (RV) involvement, due to lung parenchymal and interstitial damage and altered pulmonary haemodynamics, even in non-advanced phases of the disease. This is a consequence of hypoxic vasoconstriction of the pulmonary circulation, the use of positive end-expiratory pressure (PEEP) in mechanical ventilation, pulmonary endothelial injury, and local inflammatory thrombotic and/or thromboembolic processes. We report the case of a young man admitted with a diagnosis of COVID-19 pneumoniae with PH unrelated to viral infection and in whom partial anomalous pulmonary venous drainage (PAPVD) was eventually diagnosed.

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