Mitochondrial complex II is essential for hypoxia-induced pulmonary vasoconstriction of intra- but not of pre-acinar arteries
Authors: Norbert Weissmann
Wolfgang Kummer
Ralph T Schermuly
Renate Paddenberg
Katrin S Lips
José López-Barneo
Anna Goldenberg
Petra Faulhammer
Barbara Gries
Uwe Pfeil
Martina Tiefenbach
José I Piruat
Journal: Cardiovascular Research (2012)
Discipline: CLINICAL MEDICINE
Keywords: Alveolar hypoxia; pulmonary arterial pressure; hypoxic pulmonary vasoconstriction; succinate dehydrogenase; mitochondrial complex II
Affiliations: Institute of Anatomy and Cell Biology, Excellence Cluster Cardio-Pulmonary System, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany. 

Abstract:  Aims: Alveolar hypoxia acutely elicits contraction of pulmonary arteries, leading to a rise in pulmonary arterial pressure (PAP) and shifting blood to better ventilated areas of the lung. The molecular mechanisms underlying this hypoxic pulmonary vasoconstriction (HPV) are still incompletely understood. Here, we investigated the role of succinate dehydrogenase (SDH; synonymous to mitochondrial complex II) in HPV, with particular emphasis on regional differences along the vascular bed and consequences for PAP and perfusion-to-ventilation matching, using mutant mice heterozygous for the SDHD subunit of complex II (SDHD(+/-)). Methods and results: Western blots revealed reduced protein content of complex II subunits SDHA, SDHB, and SDHC in lungs of SDHD(+/-) mice, despite unaffected mRNA content as determined by real-time PCR. Hypoxic pulmonary vasoconstriction of small (20-50 µm) intra-acinar and larger (51-100 µm) pre-acinar arteries was evaluated by videomorphometric analysis of precision-cut lung slices. The hypoxic response was detectable in pre-acinar arteries but absent from intra-acinar arteries of SDHD(+/-) mice. In isolated perfused lungs, basal PAP and its hypoxia-induced increase were indistinguishable between both mouse strains. Arterial oxygenation was measured after provocation of regional ventilatory failure by tracheal fluid instillation in anaesthetized mice, and it declined more in SDHD(+/-) than in wild-type mice. Conclusion: SDHD is required for the formation of a stable mitochondrial complex II and it is selectively important for HPV of intra-acinar vessels. This specialized vascular segment participates in perfusion-to-ventilation matching but does not significantly contribute to the acute hypoxic rise in PAP that results from more proximal vasoconstriction. 

Retracted: No

PubPeer comments:
 *Corrigendum: Cardiovascular Research, cvaa111,Published: 01 June 2020*  The authors regret the presence of undisclosed image splicing in the representative western blots shown in Figure 3. In the original western blot experiment, the samples were not run next to each other on the gel. Thus, when the bands were collated for the paper it was necessary to splice the images together. For clarity, Figure 3 now indicates lanes that were not next to each other in the original western blot by white vertical bars. This updated figure has been added to the manuscript. This matter was investigated by the ESC Journals Family Ethics Committee, which recommended this resolution. These changes do not affect the overall scientific message of the paper. ,