Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F17%3A00487981" target="_blank" >RIV/67985823:_____/17:00487981 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1007/978-3-319-63245-2_14" target="_blank" >http://dx.doi.org/10.1007/978-3-319-63245-2_14</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/978-3-319-63245-2_14" target="_blank" >10.1007/978-3-319-63245-2_14</a>

Result language

angličtina

Original language name

Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension

Original language description

Pulmonary hypertension is a complex disease of the pulmonary vasculature, which in severe cases terminates in right heart failure. Complex remodeling of pulmonary arteries comprises the central issue of its pathology. This includes extensive proliferation, apoptotic resistance and inflammation. As such, the molecular and cellular features of pulmonary hypertension resemble hallmark characteristics of cancer cell behavior. The vascular remodeling derives from significant metabolic changes in resident cells, which we describe in detail. It affects not only cells of pulmonary artery wall, but also its immediate microenvironment involving cells of immune system (i.e., macrophages). Thus aberrant metabolism constitutes principle component of the cancer-like theory of pulmonary hypertension. The metabolic changes in pulmonary artery cells resemble the cancer associated Warburg effect, involving incomplete glucose oxidation through aerobic glycolysis with depressed mitochondrial catabolism enabling the fueling of anabolic reactions with amino acids, nucleotides and lipids to sustain proliferation. Macrophages also undergo overlapping but distinct metabolic reprogramming inducing specific activation or polarization states that enable their participation in the vascular remodeling process. Such metabolic synergy drives chronic inflammation further contributing to remodeling. Enhanced glycolytic flux together with suppressed mitochondrial bioenergetics promotes the accumulation of reducing equivalents, NAD(P)H. We discuss the enzymes and reactions involved. The reducing equivalents modulate the regulation of proteins using NAD(P)H as the transcriptional co-repressor C-terminal binding protein 1 cofactor and significantly impact redox status (through GSH, NAD(P)H oxidases, etc.), which together act to control the phenotype of the cells of pulmonary arteries. The altered mitochondrial metabolism changes its redox poise, which together with enhanced NAD(P)H oxidase activity and reduced enzymatic antioxidant activity promotes a pro-oxidative cellular status. Herein we discuss all described metabolic changes along with resultant alterations in redox status, which result in excessive proliferation, apoptotic resistance, and inflammation, further leading to pulmonary arterial wall remodeling and thus establishing pulmonary artery hypertension pathology.

Czech name

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Czech description

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Type

C - Chapter in a specialist book

CEP classification

—

OECD FORD branch

30203 - Respiratory systems

Project

<a href="/en/project/LH15071" target="_blank" >LH15071: The role of mitochondrial energy metabolism and redox regulations in pulmonary hypertension</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Book/collection name

Pulmonary Vasculature Redox Signaling in Health and Disease

ISBN

978-3-319-63244-5

Number of pages of the result

20

Pages from-to

241-260

Number of pages of the book

422

Publisher name

Springer International Publishing

Place of publication

Cham

UT code for WoS chapter

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