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Renin-Angiotensin System Proteases and the Cardiometabolic Syndrome: Pathophysiological, Clinical and Therapeutic Implications

Published on Jan 1, 2007
· DOI :10.1007/978-1-4020-6372-5_5
Guido Lastra23
Estimated H-index: 23
(University of Missouri),
Camila Manrique24
Estimated H-index: 24
(University of Missouri),
James R. Sowers83
Estimated H-index: 83
(University of Missouri)
Obesity, Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Disease (CVD) are worldwide leading causes of morbidity and mortality. Once considered as separate metabolic and hemodynamic/cardiovascular entities respectively, it has become nowadays clear that the relationship between these conditions is not coincidental, and has common pathophysiological features that allows considering both obesity and T2DM as part of the cardiovascular diseases spectrum. Furthermore, from a clinical standpoint it is also clear that cardiovascular risk factors seldom are isolated findings, but frequently present as a clustering of different conditions, including abnormalities in blood pressure, body weight, glucose homeostasis and albuminuria. The tendency of CVD risk factors to cluster has been described in the medical literature since the decade of 1920s (Avogaro et al 1967). However, the concept of Cardiometabolic Syndrome (CMS) is still evolving, and makes reference to a group of cardiovascular /metabolic risk factors, including hypertension (HTN), dysglycemia, atherogenic dyslipidemia, albuminuria and obesity, which confer an excess high risk for CVD than its individual components. Several names have been given to the condition, including Syndrome X, Dysmetabolic Syndrome, Insulin Resistance Syndrome, Metabolic Syndrome and more recently Cardiometabolic Syndrome. In addition, numerous worldwide organizations have described the CMS and have used different definition criteria, which take into account the current epidemiologic, clinic and pathophysiological evidence available about the condition. These include the National Cholesterol Education
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  • Citations (1)
Published on Oct 12, 2006in The New England Journal of Medicine 79.26
Jackie Bosch43
Estimated H-index: 43
Salim Yusuf Mb Bs DPhil Frcpc209
Estimated H-index: 209
+ 9 AuthorsR R Holman92
Estimated H-index: 92
Background Previous studies have suggested that blockade of the renin–angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension. Methods In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) an...
573 Citations Source Cite
Published on Oct 1, 2006in Advances in Chronic Kidney Disease 2.63
Guido Lastra23
Estimated H-index: 23
Camila Manrique24
Estimated H-index: 24
James R. Sowers83
Estimated H-index: 83
The epidemic of obesity experienced in both industrialized and nonindustrialized countries largely accounts for the increase in the prevalence of the cardiometabolic syndrome (CMS). Obesity and the CMS significantly increase the risk for cardiovascular disease (CVD) and chronic kidney disease (CKD). Multiple abnormalities that can lead to kidney injury have been identified in overweight and obese people, including insulin resistance, compensatory hyperinsulinemia, inappropriate activation of the...
50 Citations Source Cite
Published on Jul 3, 2006in Journal of Clinical Investigation 13.25
Takashi Kadowaki121
Estimated H-index: 121
Toshimasa Yamauchi62
Estimated H-index: 62
+ 3 AuthorsKazuyuki Tobe66
Estimated H-index: 66
Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic met...
1,895 Citations Source Cite
Published on Jul 1, 2006in Hypertension 6.82
Matthew E. Dickson4
Estimated H-index: 4
(Roy J. and Lucille A. Carver College of Medicine),
Curt D. Sigmund66
Estimated H-index: 66
(Roy J. and Lucille A. Carver College of Medicine)
Hypertension is a common and complex human disease that causes significant morbidity and mortality worldwide. Unfortunately, despite recent advances in understanding and treating hypertension, its prevalence continues to rise. Across the globe, &26% of the adult population experiences hypertension, and Kearney et al1 estimate that this could rise to &29% by the year 2025. According to the American Heart Association, one third of the United States adult population is hypertensive, and one third o...
81 Citations Source Cite
Published on May 15, 2006in Journal of Cellular Biochemistry 2.96
Seung-Hyun Ko28
Estimated H-index: 28
(Catholic University of Korea),
Oak-Kee Hong7
Estimated H-index: 7
(Catholic University of Korea)
+ 7 AuthorsKun-Ho Yoon30
Estimated H-index: 30
(Catholic University of Korea)
Pancreatic stellate cells (PSCs) are involved in pancreatic inflammation and fibrosis. Recent studies have shown that blocking the renin–angiotensin system (RAS) attenuates pancreatic inflammation and fibrosis. However, there are few data about the direct effects of high glucose on extracellular matrix (ECM) protein synthesis and angiotensin II (Ang II) induction in PSCs. PSCs were isolated from male Sprague–Dawley rats and cultured in medium containing 5.5 mM (LG group) or 27 mM D-glucose (HG g...
57 Citations Source Cite
Chris Tikellis21
Estimated H-index: 21
Mark E. Cooper109
Estimated H-index: 109
Merlin C. Thomas54
Estimated H-index: 54
Abstract Activation of the renin–angiotensin system has a pivotal role in the pathogenesis of diabetic complications. However, recent evidence suggests that it may also contribute to the development of diabetes itself. In the endocrine pancreas, all the components of an active renin–angiotensin system are present, which modulate a range of activities including local blood flow, hormone release and prostaglandin synthesis. In both types 1 and 2 diabetes, there is an up-regulation of its expressio...
47 Citations Source Cite
Published on Apr 1, 2006in Diabetes Care 13.40
Tadashi Konoshita10
Estimated H-index: 10
Shigeyuki Wakahara6
Estimated H-index: 6
+ 8 AuthorsIsamu Miyamori26
Estimated H-index: 26
OBJECTIVE —Recent studies have proved that blockade of the renin-angiotensin system (RAS) retards the progression of diabetic nephropathy, whereas hyporeninemia is known as a typical state in diabetic subjects. The purpose of this study is to determine whether expression levels of RAS differ between nondiabetic and diabetic renal tissues with accurate quantitative method. RESEARCH DESIGN AND METHODS —Subjects were 66 nondiabetic and 8 diabetic patients with biopsy-proven renal diseases. The eigh...
49 Citations Source Cite
Published on Mar 1, 2006in Diabetes Care 13.40
Carlos Lorenzo28
Estimated H-index: 28
Manuel Serrano-Ríos13
Estimated H-index: 13
(Complutense University of Madrid)
+ 6 AuthorsSteven M. Haffner115
Estimated H-index: 115
(University of Texas Health Science Center at San Antonio)
OBJECTIVE —We have carried out international comparisons of the metabolic syndrome using the International Diabetes Federation (IDF) and National Cholesterol Education Program–Adult Treatment Panel III (ATP III) definitions. This analysis could help to discern the applicability of these definitions across populations. RESEARCH DESIGN AND METHODS —Nondiabetic subjects aged 35–64 years were eligible for analysis in population-based studies from San Antonio (Mexican Americans and non-Hispanic white...
88 Citations Source Cite
Published on Feb 1, 2006in Diabetes 7.27
Kwan Yi Chu1
Estimated H-index: 1
Tung Lau1
Estimated H-index: 1
+ 1 AuthorsPo Sing Leung30
Estimated H-index: 30
We identified an angiotensin-generating system in pancreatic islets and found that exogenously administered angiotensin II, after binding to its receptors (angiotensin II type 1 receptor [AT1R]), inhibits insulin release in a manner associated with decreased islet blood flow and (pro)insulin biosynthesis. The present study tested the hypothesis that there is a change in AT1R expression in the pancreatic islets of the obesity-induced type 2 diabetes model, the db/db mouse, which enables endogenou...
150 Citations Source Cite
Published on Feb 1, 2006in European Journal of Endocrinology 4.33
R Lupi34
Estimated H-index: 34
S Del Guerra31
Estimated H-index: 31
+ 5 AuthorsPiero Marchetti65
Estimated H-index: 65
Objective: Data from prospective studies suggest a significant reduction in the risk of new diabetes from drug therapies containing angiotensin-converting enzyme (ACE) inhibitors. Since the renin-angiotensin system (RAS) has been found locally in several tissues and cells, including pancreatic islets, we hypothesized that the positive metabolic effects of ACE inhibitors may be due to a beneficial action of these compounds on insulin-secreting p-cells. Design and methods: Isolated human pancreati...
70 Citations Source Cite
Cited By1
Peter M. Abadir10
Estimated H-index: 10
(Johns Hopkins University),
Helmy M. Siragy49
Estimated H-index: 49
(University of Virginia)
Introduction: Previous studies demonstrated that stimulation of angiotensin subtype 1 receptor (AT1R) led to increased renal generation of prostaglandins E2 (PGE2) and renal inflammation. In turn, PGE2 increases AT1R activity. The conversion of PGE2 to the less active metabolite prostaglandin F2α (PGF2α) via 9-ketoreductase interrupts this feedback loop. The effects of diabetes on the interface between AT1R, PGE2 and PGF2α are not well established. We hypothesized that in diabetes, an aberrant A...
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