Involvement of Bone Marrow Cells and Neuroinflammation in Hypertension
Open accessAbstract
Rationale: Microglial activation in autonomic brain regions is a hallmark of neuroinflammation in neurogenic hypertension. Despite evidence that an impaired sympathetic nerve activity supplying the bone marrow (BM) increases inflammatory cells and decreases angiogenic cells, little is known about the reciprocal impact of BM-derived inflammatory cells on neuroinflammation in hypertension. Objective: To test the hypothesis that proinflammatory BM cells from hypertensive animals contribute to neuroinflammation and hypertension via a brain–BM interaction. Methods and Results: After BM ablation in spontaneously hypertensive rats, and reconstitution with normotensive Wistar Kyoto rat BM, the resultant chimeric spontaneously hypertensive rats displayed significant reduction in mean arterial pressure associated with attenuation of both central and peripheral inflammation. In contrast, an elevated mean arterial pressure along with increased central and peripheral inflammation was observed in chimeric Wistar-Kyoto rats reconstituted with spontaneously hypertensive rat BM. Oral treatment with minocycline, an inhibitor of microglial activation, attenuated hypertension in both the spontaneously hypertensive rats and the chronic angiotensin II–infused rats. This was accompanied by decreased sympathetic drive and inflammation. Furthermore, in chronic angiotensin II–infused rats, minocycline prevented extravasation of BM-derived cells to the hypothalamic paraventricular nucleus, presumably via a mechanism of decreased C-C chemokine ligand 2 levels in the cerebrospinal fluid. Conclusions: The BM contributes to hypertension by increasing peripheral inflammatory cells and their extravasation into the brain. Minocycline is an effective therapy to modify neurogenic components of hypertension. These observations support the hypothesis that BM-derived cells are involved in neuroinflammation, and targeting them may be an innovative strategy for neurogenic resistant hypertension therapy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Bone-marrow-derived immune cells are activated by the gut microbiota, leading to low-grade inflammation that affects the brain, ANS and the kidney via the circulation.
“Bone-marrow-derived immune cells are activated by the gut microbiota, leading to low-grade inflammation that affects the brain, ANS and the kidney via the circulation13–15.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [15]
Our research group was the first to demonstrate a contribution of the brain-gut-bone-marrow axis to blood pressure elevation.
“Our research group was the first to demonstrate a contribution of the brain-gut-bone-marrow axis to blood pressure elevation15,87,91,154–159.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [15]
Release of inflammatory immune cells from the bone marrow contributes to the pathogenesis of hypertension and chronic kidney disease.
“and the release of these inflammatory immune cells from the bone marrow contributes to the pathogenesis of hypertension and CKD15,156,189.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [15]
The immune pathway of the brain-kidney axis involves input from the CNS and/or sympathetic nervous system to the bone marrow and effects of inflammatory cells released from the bone marrow on the kidney.
“Therefore, the immune pathway of the brain-kidney axis involves input from the CNS and/or SNS to the bone marrow and the effects of inflammatory cells released from the bone marrow on the kidney.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [15]
Abnormal sympathetic drive to the bone marrow in hypertension and chronic kidney disease dramatically shifts the immune properties of haematopoietic cells to a pro-inflammatory state.
“Abnormal sympathetic drive to the bone marrow in hypertension and CKD dramatically shifts the immune properties of haematopoietic cells to a pro-inflammatory state”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [15]
Transplantation of bone marrow, gut microbiota or kidney has been demonstrated to induce disorders not only in the organs of the proposed brain-gut-kidney axis but also in the interconnected pathways of this axis.
“Consistent with our hypothesis, transplantation of bone marrow15,122, gut microbiota90 or kidney204 has been demonstrated to induce disorders not only in the organs of the proposed brain-gut-kidney axis but also in the interconnected pathways of this axis.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 60 · Cited by 181
- Authors
- Santisteban, M. M., Ahmari, N., Carvajal, J. M., Zingler, M. B., Qi, Y., Kim, S., Joseph, J., Garcia-Pereira, F., Johnson, R. D., Shenoy, V., Raizada, M. K., & Zubcevic, J.
- Affiliations
- University of Florida Health (US)
- From the Physiology and Functional Genomics, College of Medicine (M.M.S., J.M.C., M.B.Z., S.K., J.J., M.K.R.), Physiological Sciences, College of Veterinary Medicine (N.A., F.G.-P., R.D.J., J.Z.), Cardiology, College of Medicine (Y.Q.), and Pharmacodynamics, College of Pharmacy (V.S.), University of Florida, Gainesville.
- ORCID
- Venue
- Circulation Research
- Published
- 2015-07-03
- Volume
- 117
- Issue
- 2
- Pages
- 178-191
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC4490954
- OpenAlex
- W2170955240
- Cited by
- 181
- References
- 60
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 13 · 2023: 14 · 2022: 18 · 2021: 17 · 2020: 26 · 2019: 25 · 2018: 14 · 2017: 19 · 2016: 14 · 2015: 5
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001427)
- National Heart, Lung, and Blood Institute (R01HL033610, R37HL033610)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- neurogenic hypertension, neuroinflammation, bone marrow cells, microglial activation, minocycline, bone marrow chimerism, bone marrow ablation, sympathetic activity, paraventricular nucleus, MCP-1, chemokines, angiotensin II, resistant hypertension
- MeSH terms
- Angiotensin II, Animals, Bone Marrow Cells, Female, Hypertension, Male, Minocycline, Norepinephrine, Paraventricular Hypothalamic Nucleus, Radiation Chimera, Rats, Inbred SHR, Rats, Inbred WKY, Sympathetic Nervous System, Bone Marrow Transplantation, T-Lymphocyte Subsets, Microglia, Baroreflex, Chemokine CCL2, Neurogenic Inflammation, Rats, Interleukin-1beta
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
