ArticleHuman gene therapy2012
AAV-based RNAi silencing of NADPH oxidase gp91(phox) attenuates cold-induced cardiovascular dysfunction.
Article in Human gene therapy, 2012. 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.
- Cold Exposure Exacerbates Cardiac Dysfunction in a Model of Heart Failure with Preserved Ejection Fraction in Male and Female C57Bl/6J Mice.Biomedicines · 2025Article
- TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation.Antioxidants (Basel, Switzerland) · 2024Article
- Aging impairs arterial compliance via Klotho-mediated downregulation of B-cell population and IgG levels.Cellular and molecular life sciences : CMLS · 2022Article
- Estrogen inhibits renal Na-Pi Co-transporters and improves klotho deficiency-induced acute heart failure.Redox biology · 2021Article
- Activation of Orexin 1 Receptors in the Paraventricular Nucleus Contributes to the Development of Deoxycorticosterone Acetate-Salt Hypertension Through Regulation of Vasopressin.Frontiers in physiology · 2021Article
- In vivo AAV delivery of glutathione reductase gene attenuates anti-aging gene klotho deficiency-induced kidney damage.Redox biology · 2020Article
- Stem cell-derived extracellular vesicles mitigate ageing-associated arterial stiffness and hypertension.Journal of extracellular vesicles · 2020Article
- Endogenous MicroRNA Competition as a Mechanism of shRNA-Induced Cardiotoxicity.Molecular therapy. Nucleic acids · 2020Article
- AAV Delivery of Endothelin-1 shRNA Attenuates Cold-Induced Hypertension.Human gene therapy · 2017Review
- Monocrotaline-Induced Pulmonary Hypertension Involves Downregulation of Antiaging Protein Klotho and eNOS Activity.Hypertension (Dallas, Tex. : 1979) · 2016Article
- Activation of SIRT1 Attenuates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhancing AMP-Activated Protein Kinase Activity.Hypertension (Dallas, Tex. : 1979) · 2016Article
- Repetitive Electroacupuncture Attenuates Cold-Induced Hypertension through Enkephalin in the Rostral Ventral Lateral Medulla.Scientific reports · 2016Article
- Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.Journal of the American Society of Nephrology : JASN · 2016Article
- Haplodeficiency of Klotho Gene Causes Arterial Stiffening via Upregulation of Scleraxis Expression and Induction of Autophagy.Hypertension (Dallas, Tex. : 1979) · 2015Article
- In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes.Diabetes · 2015Article
- AAV delivery of tumor necrosis factor-α short hairpin RNA attenuates cold-induced pulmonary hypertension and pulmonary arterial remodeling.Hypertension (Dallas, Tex. : 1979) · 2014Article
- Genetic deficiency of anti-aging gene klotho exacerbates early nephropathy in STZ-induced diabetes in male mice.Endocrinology · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Clinical observations and epidemiological surveys indicated that the prevalence of hypertension and heart diseases is increased in cold regions or during winter. Cold exposure increased NADPH oxidase gp91(phox) protein expression in heart, kidneys, and aorta in rats. The aim of this study was to investigate if RNA interference (RNAi) silencing of gp91(phox) would attenuate cold-induced hypertension and cardiovascular and renal damage. The recombinant adeno-associated virus serotype 2 (AAV-2) vector carrying gp91(phox)-shRNA (gp91-shRNA) was constructed for inhibiting gp91(phox) protein expression in cold-exposed rats. Blood pressure (BP) was monitored using a telemetry system. BP was increased in the Control-shRNA and PBS groups within 1 week of exposure to moderate cold (5°C) and reached a plateau after 7 weeks. The cold-induced increase in BP was attenuated significantly by intravenous delivery of gp91-shRNA (1.25×10(10) particles/rat, 0.5 mL). One single dose of gp91-shRNA controlled hypertension for up to 10 weeks. In addition, gp91-shRNA reversed cold-induced vascular dysfunction. gp91-shRNA abolished the cold-induced up-regulation of gp91(phox) protein expression in heart, kidneys, and aorta, confirming effective silencing of gp91(phox). The cold-induced increases in NADPH oxidase activity and superoxide production were eliminated by silencing of gp91(phox), suggesting that the cold-induced up-regulation of NADPH oxidase activity may be attributed to the increased gp91(phox) protein expression. RNAi silencing of gp91(phox) abolished cold-induced cardiac and renal hypertrophy and attenuated aortic, coronary, and renal remodeling. The up-regulation of gp91(phox) may play a critical role in cold-induced cardiovascular dysfunction and organ damage. AAV delivery of gp91-shRNA may be a new and effective therapeutic approach for cold-related cardiovascular disorders.
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