scholarly journals Function of Adipose-Derived Mesenchymal Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension through miR-191 via Regulation of BMPR2

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Caixin Zhang ◽  
Pengbo Wang ◽  
Anaz Mohammed ◽  
Zhewen Zhou ◽  
Shuwen Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Therapeutic Strategies ◽  
Protective Effects ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a serious condition. However, prevailing therapeutic strategies are not effective enough to treat PAH. Therefore, finding an effective therapy is clearly warranted. Adipose-derived mesenchymal stem cells (ASCs) and ASCs-derived exosomes (ASCs-Exos) exert protective effects in PAH, but the underlying mechanism remains unclear. Using a coculture of ASCs and monocrotaline pyrrole (MCTP)-treated human pulmonary artery endothelial cells (HPAECs), we demonstrated that ASCs increased cell proliferation in MCTP-treated HPAECs. Results showed that ASCs-Exos improved proliferation of both control HPAECs and MCTP-treated HPAECs. In addition, by transfecting ASCs with antagomir we observed that low exosomal miR-191 expression inhibited HPAECs proliferation whereas the agomir improved. Similar results were observed in vivo using a monocrotaline (MCT)-induced PAH rat model following ASCs transplantation. And ASCs transplantation attenuated MCT-induced PAH albeit less than the antagomir treated group. Finally, we found that miR-191 repressed the expression of bone morphogenetic protein receptor 2 (BMPR2) in HPAECs and PAH rats. Thus, we conjectured that miR-191, in ASCs and ASCs-Exos, plays an important role in PAH via regulation of BMPR2. These findings are expected to contribute to promising therapeutic strategies for treating PAH in the future.

Protective effects of isorhamnetin on pulmonary arterial hypertension: in vivo and in vitro studies

2020 ◽  
Vol 34 (10) ◽  
pp. 2730-2744
Author(s):  
Zhi Chang ◽  
Jia‐ling Wang ◽  
Zhi‐cheng Jing ◽  
Ping Ma ◽  
Qing‐bing Xu ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
In Vitro Studies ◽  
Protective Effects ◽  
Pulmonary Arterial

scholarly journals Rutin Reverses Abnormal Autophagy in Hypoxic Pulmonary Arterial Hypertension via Regulation of Mitofusin 1

2021 ◽  
Author(s):  
Ming-xue Huang ◽  
Man Wang ◽  
Yu-wei Song ◽  
Yan Song ◽  
Ling Jing
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Exposure Period ◽  
Underlying Mechanism ◽  
Left Ventricular ◽  
Protective Effects ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Arterial ◽  
Mitofusin 1

Abstract Background:Recently, rutin, a citrus flavonoid occurring in many plants, has been found to be beneficial in preventing hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) from proliferating via scavenged reactive oxygen species (ROS). However, rutin’s underlying mechanism of action against PASMCs in the context of hypoxia is still unclear. Autophagy, the main intracellular degradation and recycling process, exerts a critical adaptive effect on the pathological angiogenesis associated with hypoxic pulmonary arterial hypertension (HPAH) by removing damaged mitochondria and regulating ROS production and cell proliferation. It would be useful to identify the role of rutin and its interaction with autophagy in exerting protective effects against HPAH.Methods:We chose 21 SD rats and randomly and equally divided them into three groups of normoxia, hypoxia, and hypoxia + rutin. At the end of the exposure period, we measured the right ventricular systolic pressure (RVSP), the weight of right ventricle (RV), and the ratio of RV weight to left ventricular (LV) weight plus septum (RV/LV+S) of each rat. PASMCs of the three groups of rats were isolated and cultured, and the effect of rutin on autophagy-related protein expression under hypoxia was analyzed using immunofluorescence analysis, transmission electron microscopy, western blot (WB) analysis, and siRNA design and transfection.Results:We found RVSP, RV/LV+S, and pulmonary artery wall thickness were reduced by rutin in the pulmonary arterial hypertension (PAH) animal model. WB results showed that rutin regulated expression of autophagy-related proteins. Moreover, rutin downregulated Mitofusin 1 (Mfn1) over-expression induced by hypoxia. But when Mfn1 was silenced, there was little difference in the expressions of beclin-1 (BECN-1), and other marker proteins with or without rutin.Conclusions:Rutin suppressed the abnormal autophagy of hypoxia-induced PASMCs via the regulation of the target, Mfn1. This revealed the protective effect of rutin on vascular remodeling caused by hypoxia and demonstrated how rutin could slow down the development of HPAH.

scholarly journals Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seyeon Oh ◽  
Albert Y. Jang ◽  
Sehyun Chae ◽  
Seungbum Choi ◽  
Jeongsik Moon ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Right Ventricular Function ◽  
Treated Group ◽  
Therapeutic Effects ◽  
Mesenchymal Stem Cell Therapy ◽  
Adaptive Immune Cells ◽  
Pulmonary Arterial

AbstractDespite the advancement of targeted therapy for pulmonary arterial hypertension (PAH), poor prognosis remains a reality. Mesenchymal stem cells (MSCs) are one of the most clinically feasible alternative treatment options. We compared the treatment effects of adipose tissue (AD)-, bone marrow (BD)-, and umbilical cord blood (UCB)-derived MSCs in the rat monocrotaline-induced pulmonary hypertension (PH) model. The greatest improvement in the right ventricular function was observed in the UCB-MSCs treated group. The UCB-MSCs treated group also exhibited the greatest improvement in terms of the largest decrease in the medial wall thickness, perivascular fibrosis, and vascular cell proliferation, as well as the lowest levels of recruitment of innate and adaptive immune cells and associated inflammatory cytokines. Gene expression profiling of lung tissue confirmed that the UCB-MSCs treated group had the most notably attenuated immune and inflammatory profiles. Network analysis further revealed that the UCB-MSCs group had the greatest therapeutic effect in terms of the normalization of all three classical PAH pathways. The intravenous injection of the UCB-MSCs, compared with those of other MSCs, showed superior therapeutic effects in the PH model for the (1) right ventricular function, (2) vascular remodeling, (3) immune/inflammatory profiles, and (4) classical PAH pathways.

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