ArticleCardiovascular research2018
Decreased mitochondrial respiration in aneurysmal aortas of Fibulin-4 mutant mice is linked to PGC1A regulation.
Article in Cardiovascular research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed.
- Article
- Reactive oxygen species in thoracic aortic dissection: Insights into mechanisms and disease progression.Redox biology · 2026Review
- Mitochondrial Functional Capacity Is Impaired in Angiotensin II-Infused Mice and Not Recovered by Metformin.Biomedicines · 2026Article
- Aging-AssociatedJournal of the American Heart Association · 2026Article
- Mitochondrial dysfunction in aortic aneurysm and dissection: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Proteome Differences in Smooth Muscle Cells from Diabetic and Non-Diabetic Abdominal Aortic Aneurysm Patients Reveal Metformin-Induced Mechanisms.Medical sciences (Basel, Switzerland) · 2025Article
- PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Mitochondrial Dysfunction: A New Hallmark in Hereditable Thoracic Aortic Aneurysm Development.Cells · 2025Review
- Causal relationship between mitochondrial proteins and risks of aortic aneurysms and aortic dissection: a Mendelian randomization study.Journal of cardiothoracic surgery · 2025Article
- Utilizing Integrated Bioinformatics Analysis to Explore Potential Alterations in Mitochondrial Function Within Immune Cells Associated with Thoracic Aortic Aneurysms.Bioengineering (Basel, Switzerland) · 2025Article
- Correcting mitochondrial loss mitigates NOTCH1-related aortopathy in mice.Nature cardiovascular research · 2025Article
- Decoding clinical diversity in monogenic TGFBR1 and TGFBR2 mutations: insights into the interplay of molecular mechanisms and hypomorphicity.Frontiers in cell and developmental biology · 2025Review
- Role of theGenes · 2024Review
- Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts.Biomedicines · 2024Article
- Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis.FEBS open bio · 2024Article
- Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.npj aging · 2024Article
- Bioengineered vascular grafts with a pathogenicScience translational medicine · 2024Article
- Selenoprotein deficiency disorder predisposes to aortic aneurysm formation.Nature communications · 2023Article
Corrections and comments
- Commented on by
Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aim: Thoracic aortic aneurysms are a life-threatening condition often diagnosed too late. To discover novel robust biomarkers, we aimed to better understand the molecular mechanisms underlying aneurysm formation. Methods and results: In Fibulin-4R/R mice, the extracellular matrix protein Fibulin-4 is 4-fold reduced, resulting in progressive ascending aneurysm formation and early death around 3 months of age. We performed proteomics and genomics studies on Fibulin-4R/R mouse aortas. Intriguingly, we observed alterations in mitochondrial protein composition in Fibulin-4R/R aortas. Consistently, functional studies in Fibulin-4R/R vascular smooth muscle cells (VSMCs) revealed lower oxygen consumption rates, but increased acidification rates. Yet, mitochondria in Fibulin-4R/R VSMCs showed no aberrant cytoplasmic localization. We found similar reduced mitochondrial respiration in Tgfbr-1M318R/+ VSMCs, a mouse model for Loeys-Dietz syndrome (LDS). Interestingly, also human fibroblasts from Marfan (FBN1) and LDS (TGFBR2 and SMAD3) patients showed lower oxygen consumption. While individual mitochondrial Complexes I-V activities were unaltered in Fibulin-4R/R heart and muscle, these tissues showed similar decreased oxygen consumption. Furthermore, aortas of aneurysmal Fibulin-4R/R mice displayed increased reactive oxygen species (ROS) levels. Consistent with these findings, gene expression analyses revealed dysregulation of metabolic pathways. Accordingly, blood ketone levels of Fibulin-4R/R mice were reduced and liver fatty acids were decreased, while liver glycogen was increased, indicating dysregulated metabolism at the organismal level. As predicted by gene expression analysis, the activity of PGC1α, a key regulator between mitochondrial function and organismal metabolism, was downregulated in Fibulin-4R/R VSMCs. Increased TGFβ reduced PGC1α levels, indicating involvement of TGFβ signalling in PGC1α regulation. Activation of PGC1α restored the decreased oxygen consumption in Fibulin-4R/R VSMCs and improved their reduced growth potential, emphasizing the importance of this key regulator. Conclusion: Our data indicate altered mitochondrial function and metabolic dysregulation, leading to increased ROS levels and altered energy production, as a novel mechanism, which may contribute to thoracic aortic aneurysm formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.