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Property "Has-20abstract" (as page type) with input value "Vascular-20remodeling-20and-20cellproliferation-20are-20part-20of-20the-20pathogenesis-20of-20pulmonary-20arterial-20hypertension-20(PAH).-20Mitochondria-20play-20an-20important-20role-20in-20disease-20development,-20due-20to-20their-20important-20functions-20in-20the-20regulation-20of-20reactive-20oxygen-20species-20(ROS),-20calcium-20homeostasis-20and-20apoptosis.-20Last-20but-20not-20least,-20the-20mitochondrial-20tricarboxylic-20acid-20cycle-20forms-20the-20hub-20in-20cell-20metabolism-20and-20the-20electron-20transport-20chain-20(ETC)-20acts-20as-20the-20main-20producer-20of-20adenosine-20triphosphate-20(ATP).-20The-20aim-20of-20this-20study-20was-20to-20elucidate-20the-20hypoxia-2Dinduced-20changes-20in-20mitochondrial-20respiration-20between-20normoxic-20control-20cells-20and-20hypoxic-20incubated-20cells-20with-20help-20of-20a-20modell-20of-20the-20hypoxia-2Dinduced-20PAH.-20For-20this-20purpose,-20isolated-20pulmonary-20arterial-20smooth-20muscle-20cells-20(PASMC)-20were-20incubates-20in-201-25-20or-207-25-20oxygen-20(O2)-20for-2024-20and-20for-2048-20hours.-20In-20addition,-20the-20O2-20affinity-20and-20the-20respiration-20of-20defined-20complex-20enzymes-20of-20the-20ETC-20were-20investigated.-20Complementary,-20the-20analysis-20of-20the-20messenger-20ribonucleic-20acid-20(mRNA)-20amount-20of-20various-20proteins-20of-20the-20ETC,-20the-20cell-20metabolism-20and-20the-20mitochondrial-20ROS-20metabolism-20took-20place.-20The-20measurements-20were-20carried-20out-20after-2012,-2024-20and-2048-20hours.-20Finally,-20this-20study-20aimed-20to-20investigate-20whether-20pharmacological-20intervention-20with-20dichloroacetate-20(DCA)-20can-20prevent-20hypoxia-2Dinduced-20changes-20in-20respiration-20and-20mRNA-20amount.-0A-0AIt-20could-20be-20shown-20that-20chronic-20exposure-20to-20hypoxia-20of-201-25-20O2-20leads-20to-20reduced-20respiration-20and-20reduced-20O2-20affinity-20in-20PASMC.-20At-207-25-20O2,-20only-20respiration-20was-20reduced.-20The-20activity-20of-20cytochrome-2Dc-2Doxidase-20(Cox)-20was-20reduced-20only-20after-20chronic-20exposure-20to-201-25-20O2.-20After-20chronic-20exposure-20to-20hypoxia,-20there-20were-20numerous-20changes-20in-20the-20amount-20of-20mRNA,-20so-20were-20glucose-20transporter-20(GLUT)-201-20and-20lactate-20dehydrogenase-20(LDH)-20a,-20as-20representatives-20of-20the-20cell-20metabolism-20increased.-20Succinate-20dehydrogenase-20(SDH)-20d,-20Cox8b-20an-20especially-20Cox4i2-20were-20also-20highly-20regulated.-20Furthermore,-20there-20was-20an-20increase-20in-20the-20amount-20of-20mRNA-20of-20superoxide-20dismutase-20(SOD)-202,-20as-20a-20protein-20of-20the-20ROS-20metabolism.-20The-20apoptosis-20marker-20p66-20SH2-20containing-20proto-2Doncogene-20(SHC)-20was-20decreased.-0A-0AThe-20protein-20concentration-20of-20Cox4i2-20was-20increased-20after-20exposure-20to-20hypoxia.-20After-20administration-20of-20the-20pyruvate-20dehydrogenase-20kinase-20(PDK)-201-20inhibitor-20DCA,-20the-20hypoxic-20effect-20on-20Cox-20but-20not-20on-20the-20respiration-20could-20be-20inhibited.-20By-20administration-20of-20DCA,-20the-20mRNA-20of-20LDHa-20could-20be-20further-20increased-20in-20comparison-20to-20hypoxically-20incubated-20cells-20alone.-20The-20mRNA-20of-20PDK1,-20Cox4i2-20and-20Cox8b-20was-20reduced.-20In-20conclusion,-20DCA-20could-20have-20an-20antiproliferative-20effect-20via-20a-20reduction-20of-20the-20lactate-20level-20that-20could-20possibily-20be-20used-20therapeutically." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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