Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00489816" target="_blank" >RIV/67985823:_____/18:00489816 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1089/ars.2017.7217" target="_blank" >http://dx.doi.org/10.1089/ars.2017.7217</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/ars.2017.7217" target="_blank" >10.1089/ars.2017.7217</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming

Popis výsledku v původním jazyce

Significance: The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e., macrophages) promotes a persistent inflammatory state, pathological angiogenesis, and fibrosis that are driven by metabolic reprogramming of mesenchymal and immune cells. Recent Advancements: Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism, and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH. In addition, metabolic reprogramming of macrophages is observed in PH and is characterized by distinct features, such as the induction of specific activation or polarization states that enable their participation in the vascular remodeling process. Critical Issues: Accumulation of reducing equivalents, such as NAD(P)H in PH cells, also contributes to their altered phenotype both directly and indirectly by regulating the activity of the transcriptional co-repressor C-terminal-binding protein 1 to control the proliferative/inflammatory gene expression in resident and immune cells. Further, similar to the role of anomalous metabolism in mitochondria in cancer, in PH short-term hypoxia-dependent and long-term hypoxia-independent alterations of mitochondrial activity, in the absence of genetic mutation of key mitochondrial enzymes, have been observed and explored as potential therapeutic targets. Future Directions: For the foreseeable future, short- and long-term metabolic reprogramming will become a candidate druggable target in the treatment of PH.

Název v anglickém jazyce

Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming

Popis výsledku anglicky

Significance: The molecular events that promote the development of pulmonary hypertension (PH) are complex and incompletely understood. The complex interplay between the pulmonary vasculature and its immediate microenvironment involving cells of immune system (i.e., macrophages) promotes a persistent inflammatory state, pathological angiogenesis, and fibrosis that are driven by metabolic reprogramming of mesenchymal and immune cells. Recent Advancements: Consistent with previous findings in the field of cancer metabolism, increased glycolytic rates, incomplete glucose and glutamine oxidation to support anabolism and anaplerosis, altered lipid synthesis/oxidation ratios, increased one-carbon metabolism, and activation of the pentose phosphate pathway to support nucleoside synthesis are but some of the key metabolic signatures of vascular cells in PH. In addition, metabolic reprogramming of macrophages is observed in PH and is characterized by distinct features, such as the induction of specific activation or polarization states that enable their participation in the vascular remodeling process. Critical Issues: Accumulation of reducing equivalents, such as NAD(P)H in PH cells, also contributes to their altered phenotype both directly and indirectly by regulating the activity of the transcriptional co-repressor C-terminal-binding protein 1 to control the proliferative/inflammatory gene expression in resident and immune cells. Further, similar to the role of anomalous metabolism in mitochondria in cancer, in PH short-term hypoxia-dependent and long-term hypoxia-independent alterations of mitochondrial activity, in the absence of genetic mutation of key mitochondrial enzymes, have been observed and explored as potential therapeutic targets. Future Directions: For the foreseeable future, short- and long-term metabolic reprogramming will become a candidate druggable target in the treatment of PH.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30203 - Respiratory systems

Projekt

<a href="/cs/project/LH15071" target="_blank" >LH15071: Role mitochondriálního energetického a redoxního metabolismu v rozvoji plicní hypertenze</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Antioxidants & Redox Signaling

ISSN

1523-0864

e-ISSN

—

Svazek periodika

28

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

230-250

Kód UT WoS článku

000418408800005

EID výsledku v databázi Scopus

2-s2.0-85039795555