2 lines of pulmonary artery smooth muscle cells metabolic profile (122 vs 3633C central metabolic profile)
Ontology highlight
ABSTRACT:
ORGANISM(S): Ovis Aries
TISSUE(S): Smooth Muscle
PROVIDER: ST000180 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter.
| S-EPMC5438125 | biostudies-literature
Project description:Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition characterized by single or recurrent pulmonary thromboemboli, which promote pulmonary vascular remodeling. MicroRNA (miRNA), is a small, noncoding RNA that is involved in multiple cell processes and functions and may participate in the pathogenesis of CTEPH. Our aims were to identify the miRNA expression signature in pulmonary artery smooth muscle cells (PASMCs) of CTEPH patients and to study the role of let-7d in CTEPH pathogenesis. The miRNA expression profile was analyzed by microarray in PASMCs of CTEPH and control patients. Differentially expressed miRNAs were selectively validated by stem-loop quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). The role of let-7d was identified by in silico analysis, and its effect on the proliferation of PASMCs was measured by methyl thiazolyl tetrazolium (MTT). Student's unpaired t test, the Fisher exact test, and the χ(2) test were used for statistical analysis. Eighteen miRNAs were differentially expressed in PASMCs from CTEPH patients, including 12 upregulated miRNAs and 6 downregulated miRNAs; among the latter, let-7d decreased 0.58-fold in CTEPH patients, as validated by qRT-PCR. It was found that let-7d could inhibit the proliferation of PASMCs through upregulation of p21. In conclusion, PASMCs in CTEPH patients have an aberrant miRNA profile and reduced let-7d, which could promote PASMC proliferation and may be involved in the pathogenesis of CTEPH.
| S-EPMC4070804 | biostudies-other
Project description:Transcriptional profiling of human pulmonary artery endothelial (HAPEC) and smooth muscle (PASM) cells comparing control untreated cells with cells transfected with ARSB-siRNA. Goal was to determine the effects of silenced of arylsufatase B on global gene expression in HAPEC and PASM cells.
2018-10-01 | GSE115268 | GEO
Project description:BackgroundExercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.MethodsSprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF).ResultsAt the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise.ConclusionCOPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.
| S-EPMC10106246 | biostudies-literature
Project description:Pulmonary hypertension (PH) is one of the most devastating cardiovascular diseases worldwide and it draws much attention from numerous scientists. As an indispensable part of pulmonary artery, smooth muscle cells are worthy of being carefully investigated. To elucidate the pathogenesis of PH, several theories focusing on pulmonary artery smooth muscle cells (PASMC), such as hyperproliferation, resistance to apoptosis, and cancer theory, have been proposed and widely studied. Here, we tried to summarize the studies, concentrating on the role of PASMC in the development of PH, feasible molecular basis to intervene, and potential treatment to PH.
| S-EPMC7441461 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-09-25 | GSE118363 | GEO
Project description:Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown.We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction.Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50-100 ?g/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utilization, oxygen consumption, mitochondrial mass, and Western blot analysis.Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and ?-oxidation. The functional outcome was an increase in myocyte fatty acid-substrate utilization, oxygen consumption, mitochondrial mass, PPAR? (peroxisome proliferator-activated receptor ?) protein expression, and extracellular acidosis. Treatment with a PPAR? agonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells.Data suggest that DEHP exposure results in metabolic remodeling of cardiomyocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and posttranscription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid intermediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction.
| S-EPMC3440133 | biostudies-literature
Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.
| S-EPMC8831561 | biostudies-literature
Project description:Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR‑106b‑5p on APE was demonstrated in platelet‑derived growth factor (PDGF)‑induced PASMCs in vitro and in an APE‑mouse model in vivo. The results showed that miR‑106b‑5p expression was downregulated in PDGF‑induced PASMCs and APE mice, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR‑106b‑5p agomiR, and increased following treatment with miR‑106b‑5p antagomiR. miR‑106b‑5p targeted the 3' untranslated region of NOR‑1 mRNA and reduced NOR1 expression. NOR1 overexpression reversed the effects of miR‑106‑5p on PDGF‑induced PASMCs. The functional roles of miR‑106b‑5p in PDGF‑induced PASMCs and an APE mouse‑model, and the underlying molecular mechanisms were evaluated. AgomiR‑106b‑5p improved APE‑induced mortality and pulmonary vascular proliferation in mice. These data suggest that miR‑106‑5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF‑induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.
| S-EPMC7138273 | biostudies-literature
Project description:Pulmonary hypertension (PH) is a complex multifactorial disease characterized by increased pulmonary vascular resistance and pulmonary vascular remodeling (PVR), with high morbidity, disability, and mortality. The abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is the main pathological change causing PVR. At present, clinical treatment drugs for PH are limited, which can only improve symptoms and reduce hospitalization but cannot delay disease progression and reduce survival rate. In recent years, numerous studies have shown that traditional Chinese medicine monomers (TCMs) inhibit excessive proliferation of PASMCs resulting in alleviating PVR through multiple channels and multiple targets, which has attracted more and more attention in the treatment of PH. In this paper, the experimental evidence of inhibiting PASMCs proliferation by TCMs was summarized to provide some directions for the future development of these mentioned TCMs as anti-PH drugs in clinical.
| S-EPMC10147991 | biostudies-literature