Pulmonary arterial hypertension in the modern era: The intersection of genotype and phenotype

Ruopp, N.; Maron, Bradley A.

doi:10.1016/j.healun.2019.10.003

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Cytosolic serine hydroxymethyltransferase (SHMT1) is implicated in calcification of VSMCs in hyperphosphatemia, such as in chronic kidney disease 64 . Finally, E3 ubiquitin-protein ligase RNF213 is a susceptibility allele for intracranial atherosclerosis, mutations of which are also associated with Moyamoa disease characterized by stenotic changes of the internal carotid arteries, peripheral pulmonary stenosis and pulmonary arterial hypertension 65 , 66 .…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth muscle cells from adult mouse heart

Cao

Minnier

Liu

et al. 2022

Sci Rep

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The microcirculation serves crucial functions in adult heart, distinct from those carried out by epicardial vessels. Microvessels are governed by unique regulatory mechanisms, impairment of which leads to microvessel-specific pathology. There are few treatment options for patients with microvascular heart disease, primarily due to limited understanding of underlying pathology. High throughput mRNA sequencing and protein expression profiling in specific cells can improve our understanding of microvessel biology and disease at the molecular level. Understanding responses of individual microvascular cells to the same physiological or pathophysiological stimuli requires the ability to isolate the specific cell types that comprise the functional units of the microcirculation in the heart, preferably from the same heart, to ensure that different cells have been exposed to the same in-vivo conditions. We developed an integrated process for simultaneous isolation and culture of the main cell types comprising the microcirculation in adult mouse heart: endothelial cells, pericytes, and vascular smooth muscle cells. These cell types were characterized with isobaric labeling quantitative proteomics and mRNA sequencing. We defined microvascular cell proteomes, identified novel protein markers, and confirmed established cell-specific markers. Our results allow identification of unique markers and regulatory proteins that govern microvascular physiology and pathology.

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Section: Discussionmentioning

confidence: 99%

Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth muscle cells from adult mouse heart

Cao

Minnier

Liu

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Macrophages confer an important role in pulmonary vascular pathobiology, and even trigger vascular injury by promoting apoptosis of endothelial cells, as well as enhancing smooth muscle cell hypertrophy and proliferation in PAH [ 4 , 5 ]. Although classified as a rare condition with a prevalence of 20 per 1,000,000 individuals [ 6 ], PAH represents a severe clinical condition due to the ineffectiveness of current treatments, and thus warrants additional research to unravel the associated pathophysiological mechanisms [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism

Wan,

Lu,

Liu

et al. 2023

Respir Res

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Background Bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) have been highly studied with their critical roles as carriers of therapeutic targets such as microRNAs (miRNAs) in the treatment of human diseases, including pulmonary arterial hypertension (PAH). Herein, we tried to study the potential of BMSC-EVs to deliver miR-200b for the regulation of macrophage polarization in PAH. Methods Rat models of PAH were induced with monocrotaline treatment, followed by miR-200b expression detection in lung tissues, pulmonary artery smooth muscle cells (PASMCs) and macrophages. miR-200b-containing BMSCs or miR-200b-deficient BMSCs were selected to extract EVs. Then, we assessed the changes in rats with PAH-associated disorders as well as in vitro macrophage polarization and the functions of PASMCs after treatment with BMSC-EVs. Moreover, the interaction between miR-200b, phosphodiesterase 1 A (PDE1A) was identified with a luciferase assay, followed by an exploration of the downstream pathway, cAMP-dependent protein kinase (PKA). Results miR-200b was reduced in lung tissues, PASMCs and macrophages of rats with PAH-like pathology. BMSC-EVs transferred miR-200b into macrophages, and subsequently accelerated their switch to the M2 phenotype and reversed the PAH-associated disorders. Furthermore, miR-200b carried by BMSC-EVs induced PKA phosphorylation by targeting PDE1A, thereby expediting macrophage polarization. Conclusion Our current study highlighted the inhibitory role of BMSC-EV-miR-200b in PAH formation.

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Pulmonary arterial hypertension in the modern era: The intersection of genotype and phenotype

Cited by 2 publications

References 10 publications

Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth muscle cells from adult mouse heart

Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth muscle cells from adult mouse heart

Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism

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