ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02584439 (Effect of Pharmacological Heart Rate Reduction on Visco-elastic Properties of the Arterial Wall), which is not on this map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
Effect of Pharmacological Heart Rate Reduction on Visco-elastic Properties of the Arterial Wall (BRADYVASC)
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Mapping arterial stiffness metabolic biomarkers: a bibliometric analysis.Frontiers in medicine · 2025Pooled it
- Targeting angiopoietin like-2 positive senescent cells improves cognitive impairment in adult male but not female atherosclerotic LDLrGeroScience · 2025Article
- The senolytic ABT-263 improves cognitive functions in middle-aged male, but not female, atherosclerotic LDLrGeroScience · 2025Article
- Initial in-hospital heart rate is associated with long-term survival in patients with acute ischemic stroke.Clinical research in cardiology : official journal of the German Cardiac Society · 2022Article
- Efficacy of metoprolol plus atorvastatin for carotid atherosclerosis and its influence on carotid intima-media thickness and homocysteine level.American journal of translational research · 2022Article
- Pathological Continuum From the Rise in Pulse Pressure to Impaired Neurovascular Coupling and Cognitive Decline.American journal of hypertension · 2020Review
- Impact of atherosclerotic disease on cerebral microvasculature and tissue oxygenation in awake LDLR-/-hApoB+/+ transgenic mice.Neurophotonics · 2019Article
- Systolic hypertension-induced neurovascular unit disruption magnifies vascular cognitive impairment in middle-age atherosclerotic LDLrGeroScience · 2019Article
- Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits.Journal of the American Heart Association · 2019Article
- Atherosclerosis is associated with a decrease in cerebral microvascular blood flow and tissue oxygenation.PloS one · 2019Article
- The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.Scientific reports · 2018Article
- Impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline.American journal of physiology. Heart and circulatory physiology · 2018Review
- Pulse pressure-dependent cerebrovascular eNOS regulation in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Effects of LDL Receptor Modulation on Lymphatic Function.Scientific reports · 2016Article
- Epigenetic Regulatory Effect of Exercise on Glutathione Peroxidase 1 Expression in the Skeletal Muscle of Severely Dyslipidemic Mice.PloS one · 2016Article
- Vascular endothelial dysfunction and pharmacological treatment.World journal of cardiology · 2015Review
- Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Review
- Carotid calcification in mice: a new model to study the effects of arterial stiffness on the brain.Journal of the American Heart Association · 2013Article
- Angiopoietin-like 2 promotes atherogenesis in mice.Journal of the American Heart Association · 2013Article
- Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice.Pflugers Archiv : European journal of physiology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The cardiac cycle imposes a mechanical stress that dilates elastic carotid arteries, while shear stress largely contributes to the endothelium-dependent dilation of downstream cerebral arteries. In the presence of dyslipidemia, carotid arteries stiffen while the endothelial function declines. We reasoned that stiffening of carotid arteries would be prevented by reducing resting heart rate (HR), while improving the endothelial function would regulate cerebral artery compliance and function. Thus we treated or not 3-mo-old male atherosclerotic mice (ATX; LDLr(-/-):hApoB(+/+)) for 3 mo with the sinoatrial pacemaker current inhibitor ivabradine (IVA), the β-blocker metoprolol (METO), or subjected mice to voluntary physical training (PT). Arterial (carotid and cerebral artery) compliance and endothelium-dependent flow-mediated cerebral dilation were measured in isolated pressurized arteries. IVA and METO similarly reduced (P < 0.05) 24-h HR by ≈15%, while PT had no impact. As expected, carotid artery stiffness increased (P < 0.05) in ATX mice compared with wild-type mice, while cerebral artery stiffness decreased (P < 0.05); this paradoxical increase in cerebrovascular compliance was associated with endothelial dysfunction and an augmented metalloproteinase-9 (MMP-9) activity (P < 0.05), without changing the lipid composition of the wall. Reducing HR (IVA and METO) limited carotid artery stiffening, but plaque progression was prevented by IVA only. In contrast, IVA maintained and PT improved cerebral endothelial nitric oxide synthase-dependent flow-mediated dilation and wall compliance, and both interventions reduced MMP-9 activity (P < 0.05); METO worsened endothelial dysfunction and compliance and did not reduce MMP-9 activity. In conclusion, HR-dependent mechanical stress contributes to carotid artery wall stiffening in severely dyslipidemic mice while cerebrovascular compliance is mostly regulated by the endothelium.
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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.