ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Heme biosynthesis modulation via δ-aminolevulinic acid administration attenuates chronic hypoxia-induced pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Maternal undernourishment impairs murine placental development during pregnancy.BMC pregnancy and childbirth · 2025Article
- Renal and Vascular Functional Decline in Aged Low Birth Weight Murine Adults.Kidney & blood pressure research · 2024Article
- Endothelin-1 depletion of cartilage oligomeric matrix protein modulates pulmonary artery superoxide and iron metabolism-associated mitochondrial heme biosynthesis.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.Antioxidants (Basel, Switzerland) · 2020Review
- Potential role of cartilage oligomeric matrix protein in the modulation of pulmonary arterial smooth muscle superoxide by hypoxia.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Metabolism and Redox in Pulmonary Vascular Physiology and Pathophysiology.Antioxidants & redox signaling · 2019Review
- Mitochondrial Iron in Human Health and Disease.Annual review of physiology · 2019Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Article
- Hypoxia-induced pulmonary hypertension in type 2 diabetic mice.Pulmonary circulation · 2017Article
- Redox Mechanisms Influencing cGMP Signaling in Pulmonary Vascular Physiology and Pathophysiology.Advances in experimental medicine and biology · 2017Article
- Update on novel targets and potential treatment avenues in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation of Mouse 3T3 Cells, Via PGC-1α Activation, Which Is Required for HO-1 Expression and Increased Mitochondrial Function.Stem cells and development · 2016Article
- Iron Metabolism and Vascular Remodeling: Novel Insights Provided by Transferrin-1 Receptor Depletion in Mice With Pulmonary Hypertension.American journal of hypertension · 2016Article
- Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in coronary artery soluble guanylate cyclase depletion by angiotensin II.American journal of physiology. Heart and circulatory physiology · 2016Article
- Rotenone-stimulated superoxide release from mitochondrial complex I acutely augments L-type Ca2+ current in A7r5 aortic smooth muscle cells.American journal of physiology. Heart and circulatory physiology · 2016Article
- EET-dependent potentiation of pulmonary arterial pressure: sex-different regulation of soluble epoxide hydrolase.American journal of physiology. Lung cellular and molecular physiology · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
This study examines how heme biosynthesis modulation with δ-aminolevulinic acid (ALA) potentially functions to prevent 21-day hypoxia (10% oxygen)-induced pulmonary hypertension in mice and the effects of 24-h organoid culture with bovine pulmonary arteries (BPA) with the hypoxia and pulmonary hypertension mediator endothelin-1 (ET-1), with a focus on changes in superoxide and regulation of micro-RNA 204 (miR204) expression by src kinase phosphorylation of signal transducer and activator of transcription-3 (STAT3). The treatment of mice with ALA attenuated pulmonary hypertension (assessed through echo Doppler flow of the pulmonary valve, and direct measurements of right ventricular systolic pressure and right ventricular hypertrophy), increases in pulmonary arterial superoxide (detected by lucigenin), and decreases in lung miR204 and mitochondrial superoxide dismutase (SOD2) expression. ALA treatment of BPA attenuated ET-1-induced increases in mitochondrial superoxide (detected by MitoSox), STAT3 phosphorylation, and decreases in miR204 and SOD2 expression. Because ALA increases BPA protoporphyrin IX (a stimulator of guanylate cyclase) and cGMP-mediated protein kinase G (PKG) activity, the effects of the PKG activator 8-bromo-cGMP were examined and found to also attenuate the ET-1-induced increase in superoxide. ET-1 increased superoxide production and the detection of protoporphyrin IX fluorescence, suggesting oxidant conditions might impair heme biosynthesis by ferrochelatase. However, chronic hypoxia actually increased ferrochelatase activity in mouse pulmonary arteries. Thus, a reversal of factors increasing mitochondrial superoxide and oxidant effects that potentially influence remodeling signaling related to miR204 expression and perhaps iron availability needed for the biosynthesis of heme by the ferrochelatase reaction could be factors in the beneficial actions of ALA in pulmonary hypertension.
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