Cited by 273Renin-Angiotensin System StudiesEicosanoids and Hypertension PharmacologyAdipokines, Inflammation, and Metabolic Diseases

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The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

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Putnam, Kelly, Shoemaker, Robin, Yiannikouris, Frederique, Cassis, Lisa A.·2012·American Journal of Physiology-Heart and Circulatory Physiology

DOI 10.1152/ajpheart.00796.2011PMC PMC3311482

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Abstract

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.

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Authors: Putnam, K., Shoemaker, R., Yiannikouris, F., & Cassis, L. A.
Affiliations: University of Kentucky (US)
Corresponding author: Cassis, Lisa A.
ORCID: Shoemaker, Robin
Yiannikouris, Frederique
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
DOI: 10.1152/ajpheart.00796.2011
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

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The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

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