Diaphragm Atrophy and Contractile Dysfunction in a Murine Model of Pulmonary Hypertension

Ahn, Bumsoo; Empinado, Hyacinth; Al-Rajhi, Monsour; Judge, Andrew R.; Ferreira, Leonardo F.

doi:10.1371/journal.pone.0062702

Cited by 28 publications

(38 citation statements)

References 44 publications

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“…PAH is a progressive disease characterized by the structural alterations of the pulmonary vasculature, leading to high pulmonary blood pressure [39]. The pathogenesis of PAH remains unclear, but proinflammatory cytokines such as TNF-α, TGF-β, and IL-6 are important factors in this condition.…”

Section: Discussionmentioning

confidence: 99%

Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Han

Liu³

et al. 2014

Cell Physiol Biochem

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Background: Mesenchymal stem cells are capable of self-renewal and multi-lineage differentiation. They are used extensively to treat several diseases. Traditionally, mesenchymal stem cells are cultured in serum-containing media, typically supplemented with fetal bovine serum (FBS). However, the variability of FBS is likely to skew experimental results. Although serum-free media used to expand mesenchymal stem cells has facilitated remarkable achievements, immunomodulation of these cells in under serum-free conditions is poorly understood. We hypothesized that mesenchymal stem cells expanded in serum-free media will retain powerful immunoregulatory functions in vitro and in vivo. Design and Methods: Immunosuppressive activity and the immunomodulatory cytokines produced by mesenchymal stem cells in serum-free media were characterized in vitro. Immunomodulation by serum-free mesenchymal stem cell expansion in monocrotaline-induced pulmonary hypertension was explored in vivo. Results: Similar to cells in serum-containing media, mesenchymal stem cells expanded in serum-free media inhibited proliferation and apoptosis of CD4⁺T cells. They also exhibited strong immunosuppressive activities and secreted high levels of immunomodulatory cytokines such as PGE2, IDO1, COX2, IL-6, and IL-1β, but not HGF. On the other hand, growth of mesenchymal stem cells in serum-free media attenuated pulmonary vascular remodeling and inhibited mRNA expression of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-1β, and IL-18. Conclusions: Mesenchymal stem cells in serum-free media maintained powerful immunomodulatory function in vitro and in vivo; serum-free media may replace serum-containing media for basic research and clinical applications.

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Section: Discussionmentioning

confidence: 99%

Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Han

Liu³

et al. 2014

Cell Physiol Biochem

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“…34 A recent investigation revealed a progressive decrease in body weight after experimentally induced PH in mice. 35 Those evidences suggest that wasting might be a result of PH rather than being a cause. On the other hand, cytokines may have a major role in the development of both PH and wasting at the same time.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary hypertension associates with malnutrition and body composition hemodialysis patients

2014

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Background/Aim: The prevalence of pulmonary hypertension (PH) is reported between 17 and 56% in hemodialysis (HD) patients. Pathogenesis of PH in HD patients is still unclear. Malnutrition associating impaired pulmonary function tests in HD patients previously reported. Present study aimed to investigate an association between PH and nutrition and inflammation HD patients. Patients/Methods: Total 179 HD patients (109 M, 70 F) were included. Pulmonary artery pressure (PAP) and ejection fraction (EF) percentage was determined by echocardiography after a midweek HD session. Bioimpedance analyses were performed after dialysis. Percent body fat mass truncal fat (%), total body water (%), body-mass index was determined. Serum 25-OH vitamin D, albumin, lipid parameters, C-reactive protein (CRP), calcium, phosphorus, parathyroid hormone, ferritin levels, and hemogram were studied. Results: Pulmonary hypertension (PAP 435 mmHg) was found in 48 (26.8%) of 179 patients studied. Body-mass index (BMI) was negatively correlated with PAP (r ¼ À0.34; p ¼ 0.02). HD vintage, prevalence of diabetes, sex, type of vascular access were not different between patients with PH and without PH. Patients with PH were older (68.1 ± 14.4; 61.3 ± 14.7; p ¼ 0.005). Percent body fat (19.8 ± 8.1% vs. 28.1 ± 10%; p ¼ 0.001), albumin (3.4 ± 0.5 g/dl vs. 3.9 ± 3.3 g/dl; p ¼ 0.0001), truncal fat (16.8 ± 10.7 vs. 26.4 ± 10.5; p ¼ 0.001), triglyceride (147.9 ± 88.5 vs. 182.1 ± 97.7 mg/dl; p ¼ 0.03), and total cholesterol (146.9 ± 34.5 vs. 169.5 ± 43 mg/dl; p ¼ 0.004) levels were significantly lower in patients with PH than with no PH. Logistic regression analysis revealed that increased percent body fat, albumin, and total cholesterol associate with a decreased risk of PH. Conclusion: Present study demonstrated a significant association between malnutrition and PH in HD patients. Those results should be confirmed by further prospective studies including cytokine levels and spirometric measurements.

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“…The lesions induced by MCT administration in rats are similar to those observed in certain chronic pulmonary vascular diseases in humans [44]. PH induced by MCT reproduces the loss of body weight and diaphragm muscle dysfunction seen in patients [37,45,46]. However, whereas MCT-treated rats become severely anorexic, in PH mice, the progressive loss of body weight and muscle mass arises in the absence of anorexia.…”

Section: The Monocrotaline (Mct) Model: a Pharmacological Model Of CCmentioning

confidence: 70%

“…However, whereas MCT-treated rats become severely anorexic, in PH mice, the progressive loss of body weight and muscle mass arises in the absence of anorexia. This suggests that mice might be preferred to rat in order to understand the mechanisms of diaphragm contractile dysfunction in PH without the confounding effect of anorexia induced by MCT [45].…”

Section: The Monocrotaline (Mct) Model: a Pharmacological Model Of CCmentioning

confidence: 99%

Animal models of cardiac cachexia

Molinari

Malara

Mollace

et al. 2016

International Journal of Cardiology

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Diaphragm Atrophy and Contractile Dysfunction in a Murine Model of Pulmonary Hypertension

Cited by 28 publications

References 44 publications

Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Serum-Free Media and the Immunoregulatory Properties of Mesenchymal Stem CellsIn VivoandIn Vitro

Pulmonary hypertension associates with malnutrition and body composition hemodialysis patients

Animal models of cardiac cachexia

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