ArticleLaboratory investigation; a journal of technical methods and pathology2009
Murine cardiac mtDNA: effects of transgenic manipulation of nucleoside phosphorylation.
Article in Laboratory investigation; a journal of technical methods and pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Antiviral Drugs in HIV and Cardiovascular Disease: Mechanistic Insights and Clinical Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Zidovudine-Mediated Autophagy Inhibition Enhances Mitochondrial Toxicity in Muscle Cells.Antimicrobial agents and chemotherapy · 2019Article
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
- AZT-induced mitochondrial toxicity: an epigenetic paradigm for dysregulation of gene expression through mitochondrial oxidative stress.Physiological genomics · 2015Article
- Aging and HIV/AIDS: pathogenetic role of therapeutic side effects.Laboratory investigation; a journal of technical methods and pathology · 2014Review
- Thymidine kinase and mtDNA depletion in human cardiomyopathy: epigenetic and translational evidence for energy starvation.Physiological genomics · 2013Article
- Transgenic mouse model with deficient mitochondrial polymerase exhibits reduced state IV respiration and enhanced cardiac fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2013Article
- The role of transporters in the toxicity of nucleoside and nucleotide analogs.Expert opinion on drug metabolism & toxicology · 2012Review
- Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters.Laboratory investigation; a journal of technical methods and pathology · 2011Article
- Absence of mitochondrial toxicity in hearts of transgenic mice treated with abacavir.Cardiovascular toxicology · 2010Article
- Transgenic cardiac-targeted overexpression of human thymidylate kinase.Laboratory investigation; a journal of technical methods and pathology · 2010Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial toxicity results from pyrimidine nucleoside reverse transcriptase inhibitors (NRTIs) for HIV/AIDS. In the heart, this can deplete mitochondrial (mt) DNA and cause cardiac dysfunction (eg, left ventricle hypertrophy, LVH). Four unique transgenic, cardiac-targeted overexpressors (TGs) were generated to determine their individual impact on native mitochondrial biogenesis and effects of NRTI administration on development of mitochondrial toxicity. TGs included cardiac-specific overexpression of native thymidine kinase 2 (TK2), two pathogenic TK2 mutants (H121N and I212N), and a mutant of mtDNA polymerase, pol-gamma (Y955C). Each was treated with antiretrovirals (AZT-HAART, 3 or 10 weeks, zidovudine (AZT) + lamivudine (3TC) + indinavir, or vehicle control). Parameters included left ventricle (LV) performance (echocardiography), LV mtDNA abundance (real-time PCR), and mitochondrial fine structure (electron microscopy, EM) as a function of duration of treatment and presence of TG. mtDNA abundance significantly decreased in Y955C TG, increased in TK2 native and I212N TGs, and was unchanged in H121N TGs at 10 weeks regardless of treatment. Y955C and I212N TGs exhibited LVH during growth irrespective of treatment. Y955C TGs exhibited cardiomyopathy (CM) at 3 and 10 weeks irrespective of treatment, whereas H121N and I212N TGs exhibited CM only after 10 weeks AZT-HAART. EM features were consistent with cardiac dysfunction. mtDNA abundance and cardiac functional changes were related to TG expression of mitochondrially related genes, mutations thereof, and NRTIs.
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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.