The DOI matches its Crossref record; 125 of the 125 references it cites were found in a registry or an index.
The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome
Open accessAbstract
The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.
Overview
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
Verification
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?
In the citing paper
“2) activation of the renin-angiotensin-aldosterone system (RAAS)”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Alberti, K. G. M. M., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., Fruchart, J.-C., James, W. P. T., Loria, C. M., & Smith, S. C. (2009) · Circulation · doi:10.1161/circulationaha.109.192644 · Cited by 14,860
Benson, S. C., Pershadsingh, H. A., Ho, C. I., Chittiboyina, A. G., Desai, P. V., Pravenec, M., Qi, N., Wang, J., Avery, M. A., & Kurtz, T. W. (2004) · Hypertension · doi:10.1161/01.hyp.0000123072.34629.57 · Cited by 1,076
Synthetic LXR ligand inhibits the development of atherosclerosis in mice
Joseph, S. B., McKilligin, E., Pei, L., Watson, M. A., Collins, A. R., Laffitte, B. A., Chen, M., Noh, G. J., Goodman, J., Hagger, G. N., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112059299 · Cited by 965
Effect of ramipril on the incidence of diabetes
(2006) · New England Journal of Medicine · doi:10.1056/nejmoa065061 · Cited by 737
Angiotensin Type 1 Receptor Blockers Induce Peroxisome Proliferator–Activated Receptor-γ Activity
Schupp, M., Janke, J., Clasen, R., Unger, T., & Kintscher, U. (2004) · Circulation · doi:10.1161/01.cir.0000127955.36250.65 · Cited by 707
Effect of valsartan on the incidence of diabetes and cardiovascular events
(2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001121 · Cited by 660
Weight Loss and the Renin-Angiotensin-Aldosterone System
Engeli, S., Böhnke, J., Gorzelniak, K., Janke, J., Schling, P., Bäder, M., Luft, F. C., & Sharma, A. M. (2005) · Hypertension · doi:10.1161/01.hyp.0000154361.47683.d3 · Cited by 627
Functional and Structural Changes in the Kidney in the Early Stages of Obesity
HENEGAR, J. R., BIGLER, S. A., HENEGAR, L. K., TYAGI, S. C., & HALL, J. E. (2001) · Journal of the American Society of Nephrology · doi:10.1681/asn.v1261211 · Cited by 549
Ramipril and the Development of Diabetes
Yusuf, S. (2001) · JAMA · doi:10.1001/jama.286.15.1882 · Cited by 541
Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation
Massiéra, F., Bloch-Faure, M., Ceiler, D. L., Murakami, K., Fukamizu, A., Gasc, J., Quignard‐Boulangé, A., Négrel, R., Ailhaud, G. P., Seydoux, J., et al. (2001) · The FASEB Journal · doi:10.1096/fj.01-0457fje · Cited by 505
Flagged first, then by citations
Research works printed but not linked: 8
- Achard V, 2011, J Endocrinol Invest
- Al-Mallah M, 2010, Cardiol J, 17, 448
- Chappell MC, 2001, JOP, 2, 33
- de Luis DA, 2010, Nutr Hosp, 25, 275
- Kyvelou SM, 2006, Hellenic J Cardiol, 47, 21
- Liu C, 2011, Acta Diabetol
- Paolisso G, 1992, J Hum Hypertens, 6, 175
- Toma I, 2008, J Clin Invest, 118, 2526
Cited by
Sorted by citations
Items 201–273 of 273
Angiotensin-converting enzyme 2 and its potential protective effect upon heart
Melaku, L. S. (2018) · Archives of Medicine and Health Sciences · doi:10.4103/amhs.amhs_44_17 · Cited by 2
1166A>C polymorphism of the AGTR1 gene as a marker metabolic disorders in the North residents
Bezmenova, I. N., & Averyanova, I. V. (2024) · Obesity and metabolism · doi:10.14341/omet12986 · Cited by 2
Toth, D. D., Souder, C., Patuel, S. J., English, C. D., Konig, I., Ivantsova, E., Malphurs, W., Watkins, J., Costa, K. A., Bowden, J. A., et al. (2024) · Biomolecules · doi:10.3390/biom14080974 · Cited by 2
Sex and Age Differences in the Impact of Metabolic Syndrome on Heart Failure Development
Kim, T., Kim, D. Y., Kim, H., & Kim, S. H. (2024) · Metabolites · doi:10.3390/metabo14120653 · Cited by 2
Gene Therapy for Diabetic Retinopathy – Targeting the Renin-Angiotensin System
Li, Q., Verma, A., Zhu, P., Lei, B., Qiu, Y., Nakagawa, T., Mohan, K., & William, W. (2013) · InTech eBooks · doi:10.5772/52702 · Cited by 2
Ji, L., Zhi, X., Lu, J., Guo, X., Yang, W., Jia, W., Zou, D., Zhou, Z., Ji, Q., Zhu, D., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103507 · Cited by 2
Stanley, W. C., & Keehan, K. H. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00082.2013 · Cited by 2
Evaluation of serum lipid profile of hypertensives in Niger-Delta, Nigeria
Bini, N., Adu, E., Inedi, A. F., Dike, M. N., Iyekekpolor, J., & Amag, R. U. (2014) · International Journal of Infectious and Tropical Diseases · doi:10.14194/ijitd.1.2.2 · Cited by 2
Angiotensin II Contributes to the Pathophysiology of Heart Failure
Ali, S. M. R. (2018) · Open Access Journal of Pharmaceutical Research · doi:10.23880/oajpr-16000169 · Cited by 2
Effects of Laparoscopic Sleeve Gastrectomy on Hypertensive Morbidly Obese Patients
Ali, H. A. A., El-Syed, M. K., & Reihan, M. S. (2019) · The Egyptian Journal of Hospital Medicine · doi:10.21608/ejhm.2019.28681 · Cited by 2
Yaşar, E., Yaşar, M. M., Doğru, S., Yaraş, N., & Eroğlu, E. (2023) · Journal of Computational Biophysics and Chemistry · doi:10.1142/s273741652350031x · Cited by 1
Aluko, E. O., Ben, E. E., & Bassey, G. E. (2025) · Cardiovascular & Hematological Agents in Medicinal Chemistry · doi:10.2174/0118715257375839250811064453 · Cited by 1
Henry, A., Vanalderwiert, L., Oszust, F., Wahart, A., Berrio, D. A. C., Brauchle, E., Schenke‐Layland, K., Brinckmann, J., Steenbock, H., Debelle, L., et al. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1648727 · Cited by 1
Metabolic syndrome and heart failure
Lopatin, Y. M. (2025) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2025-6540 · Cited by 1
Doma, M., Pintado, J. J. L., Atwal, A., Jesus, A. L., Zahrawi, F. M., Saleh, I., Gammal, A. E., Maharm, Z., Ramadan, A., Vlassis, B., et al. (2025) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000002637 · Cited by 2
Flück, M., Gasser, B. A., & Giraud, M.-N. (2026) · The FASEB Journal · doi:10.1096/fj.202504082r · Cited by 1
Abbes, N., Mohan, U. P., Mobasheran, P., Dinh, P., Abbas, M., Lazartigues, E. D., & Yue, X. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00345.2026 · Cited by 1
Angiotensin IV induced contractions in human jejunal wall musculature in vitro
Malinauskas, M., Stankevıčıus, E., & Casselbrant, A. (2014) · Peptides · doi:10.1016/j.peptides.2014.07.008 · Cited by 1
Özcan, Ö. U., Üstün, E. E., Güleç, S., Gerede, D. M., Göksülük, H., Vurgun, V. K., Kaya, C. T., & Erol, Ç. (2015) · Cardiology Journal · doi:10.5603/cj.a2014.0101 · Cited by 1
Serum lipid abnormalities in type 2 diabetes mellitus
Adu, M. E. (2014) · African Journal of Cellular Pathology · doi:10.5897/ajcpath14.014 · Cited by 1
Catarata, M. J., Medeiros, R., Oliveira, M. J., Pêgo, A., Frade, J. G., Martins, M. F., Cordeiro, C. R. R., Herth, F. J. F., Thomas, M., Kriegsmann, M., et al. (2020) · Cancers · doi:10.3390/cancers12123834 · Cited by 1
Tkaczenko, H., Tomin, V. I., Osmólska, U., & Kurhaluk, N. (2023) · Optics & Laser Technology · doi:10.1016/j.optlastec.2023.110116 · Cited by 2
Bisseneva, A., Li, K. G., Pogossyan, G. P., & Protas, V. (2023) · OnLine Journal of Biological Sciences · doi:10.3844/ojbsci.2024.32.40 · Cited by 1
Angiotensin Converting Enzyme Inhibitors and AT1 Antagonists for Treatment of Hypertension
Morisco, C., & Trimarco, B. (2014) · Springer eBooks · doi:10.1007/978-3-319-09788-6_1 · Cited by 1
Putnam, K. (2012) · UKnowledge (University of Kentucky) · Cited by 1
Self-citationAmend, G., Baird, A. D., Baradaran, N., Bele, U., Breyer, B. N., Cito, G., Drake, M. J., Henderson, E. J., Joinson, C. J., Rivas, J. G., et al. (2019) · Springer eBooks · doi:10.1007/978-3-030-27747-5_7 · Cited by 1
Ribeiro, A. M. D. J. S. D. A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.89193 · Cited by 1
Sistema Renina Angiotensina, para além da Hipertensão Arterial
Pereira, S. P. T. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 1
Dyslipidemia in Diabetes Mellitus and Chronic Kidney Disease
Krikorian, A., & Chaiban, J. T. (2014) · Springer eBooks · doi:10.1007/978-1-4939-0793-9_12
Blood Pressure Regulation by the Endocannabinoid System in Conditions Associated with Hypertension
Schaich, C. L. (2014) · WakeSpace Scholarship (Wake Forest University)
Ylipainon aiheuttamat muutokset hemodynamiikan säätelyssä
Ketola, I. (2016) · Tampere University Institutional Repository (Tampere University)
Buchmann, N., Norman, K., Demuth, I., & Steinhagen‐Thiessen, E. (2016) · Journal of Laboratory Medicine · doi:10.1515/labmed-2016-0032
Pipkin, F. B., & Loughna, P. V. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-416045-3.00018-2
Durmić, T., Mihailović, Z., Zdravkovic, M. D., & Stojković, O. (2016) · Medicinski podmladak · doi:10.5937/mp67-12811
THE EFFECT OF EZETIMIBE ON GLYCEMIC PARAMETER IN IRAQI WOMEN WITH METABOLIC SYNDROME.
IJAR, Allami, A., Al‐Jawad, F. H., IJAR, yaseen, Y. O., IJAR, ShamukhAlsaedi., M., & IJAR (2017) · International Journal of Advanced Research · doi:10.21474/ijar01/4025
Role of Cathepsin G in Atherosclerosis
Rafatian, N. (2013) · uO Research (University of Ottawa) · doi:10.20381/ruor-6368
Role of heme oxygenase in cardiomyopathy in obese Zucker fatty rats
Tiwari, S. (2016) · HARVEST (University of Saskatchewan)
The Role of Palmitoleate in Hypertension and Cardiac Hypertrophy
Bairwa, S. C. (2017) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3p26qh7t
Wakui, H., Azushima, K., Ohki, K., Uneda, K., Kobayashi, R., Suzuki, T., & Tamura, K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816093-0.00016-1
Patney, V., Ardhanari, S., & Whaley‐Connell, A. T. (2019) · Springer eBooks · doi:10.1007/978-3-319-97765-2_1
Badin, J. K. (2019) · IUScholarWorks (Indiana University) · doi:10.7912/c2/2028
Arterial hypertension and coronary heart disease: the place of angiotensin II receptor antagonists
Таратухин, Е. О. (2012) · CARDIOVASCULAR THERAPY AND PREVENTION · doi:10.15829/1728-8800-2012-6-78-80
Obesity, hypertension, and preeclampsia
Broughton-Pipkin, F., & Loughna, P. V. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817921-5.00013-8
A Comparative Study between the Effect of Ropinirole and Metformin on Metabolic Syndrome in Women
Al‐Jawad, F. H., yaseen, Y. O., Gatea, F. K., & Hoshi, A. K. (2020) · Scholars Academic Journal of Pharmacy · doi:10.36347/sajp.2020.v09i08.001
Hussain, T. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734297361.793553253
Adventitia and perivascular adipose tissue—the integral unit in vascular disease
Yang, Z., & Ming, X. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780198755777.003.0020
Losartan prevents mesenteric vascular bed alterations in high-fat diet fed rats
Lee, H. J., Cantú, S. M., Primo, M. Á., Peredo, H. A., Donoso, A. S., Puyó, A. M., & Choi, M. R. (2021) · Clínica e Investigación en Arteriosclerosis (English Edition) · doi:10.1016/j.artere.2021.01.001
Guimarães, J. P. T. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2021.tde-04052022-144336
Zainal, A. A., & Chalaby, L. A. (2022) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2022.10017
Bioactive compounds in neglected and underutilized plants
de Souza, T. C. L. (2019) · doi:10.47749/t/unicamp.2019.1162242
Renal-Derived Human sPRR Does Not Increase Blood Pressure in High Fat Diet MicePreprint
Arthur, G., Biel, K., Osborn, J. L., Hinds, T. D., Gong, M. C., & Loria, A. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.30.577981
Choice of antihyprtensive therapy at varios stages of metabolically associated lever disease
Lazebnik, L. B., Чихирева, Л. Н., Chikhirev, O. A., & Li, E. D. (2024) · Экспериментальная и клиническая гастроэнтерология · doi:10.31146/1682-8658-ecg-219-11-52-61
Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19?
Cüre, M. C., & Cüre, E. (2024) · Current Pharmaceutical Design · doi:10.2174/0113816128300162240322075423
Henry, A., Vanalderwiert, L., Wahart, A., Berrio, D. A. C., Brauchle, E., Schenke‐Layland, K., Brinckmann, J., Steenbock, H., Debelle, L., Six, I., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4147049/v1
Editorial related to the special issue: “Extrarenal functions of the renin‐angiotensin‐system”
Touyz, R. M., & Steckelings, U. M. (2025) · Acta Physiologica · doi:10.1111/apha.70027
Marques, P. L., Galac, S., Mateus, L. M., & Leal, R. O. (2025) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2025.106955 · Cited by 1
Liu, Z., Jin, P., Liu, Y., Zhang, Z., Wu, X., Weng, M., Cao, S., Wang, Y., Zeng, C., Yang, R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26036468
Dou, J., Guo, C., Wang, Y., Peng, Z., Wu, R., Li, Q., Zhao, H., Song, S., Sun, X., & Wei, J. (2024) · Figshare · doi:10.6084/m9.figshare.24532301
Kim, K., Moon, J. H., Ahn, C. H., & Lim, S. (2024) · Figshare · doi:10.6084/m9.figshare.26574394
Dou, J., Guo, C., Wang, Y., Peng, Z., Wu, R., Li, Q., Zhao, H., Song, S., Sun, X., & Wei, J. (2023) · Figshare · doi:10.6084/m9.figshare.24531978
Alsiraj, Y., Putnam, K., Brunner, S. I., English, V. L., Ensor, M., & Cassis, L. A. (2025) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2026.03.011
Self-citationComprehensive Management Strategies for Cardiovascular–Kidney–Metabolic Syndrome
Ouatu, A., & Buliga-Finiș, O. N. (2025) · Springer eBooks · doi:10.1007/978-3-032-11445-7_18
Shen, K., Lin, S.-Y., Hao, C., Chen, F.-C., Su, H.-J., Chen, Y.-M., & Lin, H.-L. (2026) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgag002
ACE2 associates with insulin-responsive GLUT4 dynamics in adipocytesPreprint
Takeru, F., Moriyama, N., Sato, H., Nishi, H., Gould, G. W., & Kanzaki, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.10.710920
Ribeiro, M. V. G., Ferreira, A. R. O., Barbosa, L. F., Lopes, G. K. G., Piovan, S., Saavedra, L. P. J., Raposo, S. R., Gomes, R. M., Malta, A., Almeida, D. L., et al. (2026) · Nutrition Research · doi:10.1016/j.nutres.2026.03.013
Abebe, G., Belete, M., & Kassaw, A. B. (2026) · Scientific Reports · doi:10.1038/s41598-026-47415-8
Afşar, B., Kanbay, M., & Afşar, R. E. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106674
Liu, X., Chen, W., Li, W., Chen, Y., & Huang, R. (2026) · BMC Cardiovascular Disorders · doi:10.1186/s12872-026-05909-3
Ghasemi-Tarie, R., Esteghamati, A., Rakhshan, K., Esteghamati, S., & Keshavarz, M. (2026) · Biomedicines · doi:10.3390/biomedicines14071533
Metadata
- Authors
- Putnam, K., Shoemaker, R., Yiannikouris, F., & Cassis, L. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Cassis, Lisa A.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2012-03-15
- Volume
- 302
- Issue
- 6
- Pages
- H1219-H1230
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC3311482
- OpenAlex
- W2137543153
- Cited by
- 273
- References
- 125
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 23 · 2023: 17 · 2022: 13 · 2021: 17 · 2020: 16 · 2019: 13 · 2018: 20 · 2017: 18 · 2016: 22 · 2015: 21 · 2014: 25 · 2013: 27 · 2012: 12
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl073085-13)
- National Heart, Lung, and Blood Institute (R01-HL-073085, HL-073085)
- National Institute of General Medical Sciences (P20GM103527)
- National Center for Research Resources (P20RR021954)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- renin-angiotensin system, metabolic syndrome, dyslipidemia, hypertension, insulin resistance, impaired glucose tolerance, angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, Mas receptor, angiotensin II, cholesterol metabolism, oxidative stress, inflammation, adipocytes, pancreatic islet cells, angiotensin receptor blockers, ACE inhibitors
- MeSH terms
- Angiotensin-Converting Enzyme Inhibitors, Animals, Blood Glucose, Blood Pressure, Homeostasis, Humans, Hypertension, Insulin Resistance, Renin-Angiotensin System, Metabolic Syndrome, Glucose Metabolism Disorders, Angiotensin II Type 1 Receptor Blockers, Dyslipidemias, Lipid Metabolism
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
