ArticleArteriosclerosis, thrombosis, and vascular biology2010
Simvastatin decreases endothelial progenitor cell apoptosis in the kidney of hypertensive hypercholesterolemic pigs.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
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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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review.Stem cell reviews and reports · 2016Pooled it
- Endothelial Progenitor Cells: Disease Markers and Potential Therapy in Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Review
- Potentials of Natural Antioxidants in Reducing Inflammation and Oxidative Stress in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- The impact of hypoxia preconditioning on mesenchymal stem cells performance in hypertensive kidney disease.Stem cell research & therapy · 2024Article
- Kidney Intrinsic Mechanisms as Novel Targets in Renovascular Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis.Stem cells (Dayton, Ohio) · 2023Article
- Article
- Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity.Marine drugs · 2020Article
- Novel therapeutic strategies for renovascular disease.Current opinion in nephrology and hypertension · 2019Review
- Emerging Paradigms in Chronic Kidney Ischemia.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Hypercholesterolemia Impairs Nonstenotic Kidney Outcomes After Reversal of Experimental Renovascular Hypertension.American journal of hypertension · 2016Article
- Role of the Renal Microcirculation in Progression of Chronic Kidney Injury in Obesity.American journal of nephrology · 2016Review
- Paradigm Shifts in Atherosclerotic Renovascular Disease: Where Are We Now?Journal of the American Society of Nephrology : JASN · 2015Review
- Obesity and renovascular disease.American journal of physiology. Renal physiology · 2015Review
- Chronic renal ischemia in humans: can cell therapy repair the kidney in occlusive renovascular disease?Physiology (Bethesda, Md.) · 2015Review
- Gained in translation: protective paradigms for the poststenotic kidney.Hypertension (Dallas, Tex. : 1979) · 2015Review
- Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease.Stem cell research & therapy · 2015Article
- Mitochondria: a pathogenic paradigm in hypertensive renal disease.Hypertension (Dallas, Tex. : 1979) · 2015Review
- Sildenafil ameliorates oxidative stress and DNA damage in the stenotic kidneys in mice with renovascular hypertension.Journal of translational medicine · 2014Article
- Renovascular hypertension leads to DNA damage and apoptosis in bone marrow cells.DNA and cell biology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveHypertension and hypercholesterolemia might interfere with renal repair mechanisms. We hypothesized that simvastatin improves the survival of endothelial progenitor cells (EPC) in the renal microenvironment imposed by concurrent renovascular hypertension and dietary hypercholesterolemia (HTC). METHODS AND
resultsPigs were studied after 12 weeks of no intervention (n=6), HTC (n=6), or HTC+ oral simvastatin supplementation (80 mg/day, n=5). EPC were also isolated and studied in vitro after exposure to the proapoptotic oxidized low-density lipoprotein with or without coincubation with simvastatin. Renal hemodynamics, function, and endothelial function were evaluated in vivo, and the number of CD34+/KDR+ EPC, apoptosis, oxidative stress, inflammation, and fibrosis in renal tissue studied ex vivo. Compared with normal kidney, the HTC kidney showed endothelial dysfunction and increased oxidative stress, interstitial macrophage filtration, and fibrosis. The number of EPC in the kidney increased, as did their apoptosis (0.85+/-0.24% versus 0.22+/-0.07%, P<0.05 versus normal). Simvastatin did not affect blood pressure, cholesterol levels, basal renal function, or number of renal EPC in HTC, but it improved endothelial function; blunted renal oxidative stress, inflammation, and fibrosis; and attenuated EPC apoptosis (to 0.37+/-0.09%, P<0.05 versus HTC). Simvastatin also significantly decreased oxidized low-density lipoprotein-induced EPC apoptosis in vitro.
conclusionEPC are recruited but undergo apoptosis in the HTC kidney, likely because of a hostile microenvironment. Simvastatin rescues renal repair mechanisms in HTC and counteracts renal damage, which may account for its protective effects on the kidney during exposure to cardiovascular risk factors.
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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 Socratic graph.