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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 Lastra22
Estimated H-index: 22
(University of Missouri),
Camila Manrique23
Estimated H-index: 23
(University of Missouri),
James R. Sowers78
Estimated H-index: 78
(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
  • References (90)
  • Cited By (1)
Published on Sep 1, 2005in Journal of the American College of Cardiology 16.83
Hussam Abuissa7
Estimated H-index: 7
Philip G. Jones41
Estimated H-index: 41
+ 1 AuthorsJames H. O'Keefe46
Estimated H-index: 46
Objectives We sought to investigate the role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in preventing the new onset of type 2 diabetes mellitus. Background Diabetes is a public health problem of epidemic proportions and its prevalence is on the rise. The typical American born today has a one in three chance of developing type 2 diabetes. This diagnosis is associated with an adverse cardiovascular prognosis and is considered the risk equivalent of e...
359 Citations Source Cite
Published on Jan 1, 1996in American Journal of Hypertension 3.05
Gaspare Parrinello22
Estimated H-index: 22
(University of Palermo),
Rosario Scaglione21
Estimated H-index: 21
(University of Palermo)
+ 6 AuthorsGiuseppe Licata44
Estimated H-index: 44
(University of Palermo)
33 Citations
Published on May 1, 2001in American Journal of Pathology 4.07
Marta Ruiz-Ortega50
Estimated H-index: 50
Óscar Lorenzo27
Estimated H-index: 27
+ 2 AuthorsJesús Egido77
Estimated H-index: 77
Recent studies have pointed out the implication of angiotensin II (Ang II) in various pathological settings. However, the molecular mechanisms and the AngII receptor (AT) subtypes involved are not fully identified. We investigated whether AngII elicited the in vivo activation of nuclear transcription factors that play important roles in the pathogenesis of renal and vascular injury. Systemic infusion of Ang II into normal rats increased renal nuclear factor (NF)-κB and AP-1 binding activity that...
154 Citations Source Cite
Published on Dec 9, 1994in Journal of Biological Chemistry 4.01
Siv A. Hjorth21
Estimated H-index: 21
Hans T. Schambye6
Estimated H-index: 6
+ 1 AuthorsThue W. Schwartz80
Estimated H-index: 80
Abstract To locate essential determinants for angiotensin II binding, we have performed a systematic mutational analysis of the exterior domain of the AT1 receptor. Receptor mutants, deficient in peptide binding, were analyzed using radiolabeled nonpeptide ligand as an important tool. Two independent strategies for mutagenesis were employed: conservative segment exchange and point mutagenesis of evolutionarily conserved residues. Results from the conservative segment exchange in which 6-17 resid...
151 Citations
J. M. Burson2
Estimated H-index: 2
(University of Iowa),
G. Aguilera1
Estimated H-index: 1
(University of Iowa)
+ 1 AuthorsCurt D. Sigmund66
Estimated H-index: 66
(University of Iowa)
At least two distinct genes (AT1A and AT1B) encode type 1 angiotensin II (AT1) receptors in rodents. Receptor binding and Northern blot analysis have clearly demonstrated the presence of AT1 receptors and AT1-receptor mRNA in many tissues but fail to differentiate which type 1 receptor subtype is expressed. A reverse-transcriptase polymerase chain reaction restriction fragment length polymorphism (RT-PCR-RFLP) assay was developed to differentiate the expressed mRNA by subtype. Expression of AT1A...
185 Citations Source Cite
Published on Apr 1, 1977in Physiological Reviews 24.01
M J Peach1
Estimated H-index: 1
1,041 Citations Source Cite
Lisa A. Cassis52
Estimated H-index: 52
(University of Kentucky),
Dana E. Marshall1
Estimated H-index: 1
(University of Kentucky)
+ 2 AuthorsRobert A. Lodder25
Estimated H-index: 25
(University of Kentucky)
Previous studies in our laboratory have implicated adipose tissue as a potential site for local angiotensin II (ANG II) synthesis. However, functions of ANG II in adipose tissue and the impact of ANG II on body weight regulation are not well defined. To study the effect of ANG II on body weight, a chronic ANG II infusion model was used. In study 1, a low dose of ANG II (175 ng ⋅ kg−1 ⋅ min−1) was infused into rats for 14 days. Plasma ANG II levels were not elevated after 14 days of infusion. ANG...
94 Citations Source Cite
Colin Berry57
Estimated H-index: 57
(University of Glasgow),
Rhian M. Touyz92
Estimated H-index: 92
(Université de Montréal)
+ 2 AuthorsD. G. Johns1
Estimated H-index: 1
(Boston University)
Angiotensin II (ANG II) is a pleiotropic vasoactive peptide that binds to two distinct receptors: the ANG II type 1 (AT1) and type 2 (AT2) receptors. Activation of the renin-angiotensin system (RAS) results in vascular hypertrophy, vasoconstriction, salt and water retention, and hypertension. These effects are mediated predominantly by AT1 receptors. Paradoxically, other ANG II-mediated effects, including cell death, vasodilation, and natriuresis, are mediated by AT2 receptor activation. Our und...
190 Citations Source Cite
Published on Apr 1, 2000in The American Journal of Clinical Nutrition 6.55
Bret H. Goodpaster79
Estimated H-index: 79
(University of Pittsburgh),
F. L. Thaete4
Estimated H-index: 4
(University of Pittsburgh),
David E. Kelley76
Estimated H-index: 76
(University of Pittsburgh)
Background: Adipose tissue (AT) content of the thigh is generally not considered to be associated with insulin resistance (IR), but it is unclear whether the distribution of AT in the thigh is a determinant of IR. Objective: We investigated whether subcompartments of AT within the thigh are determinants of IR. Design: Midthigh AT, muscle composition, and insulin sensitivity were compared in 11 obese patients with type 2 diabetes mellitus (DM); 40 obese, glucose-tolerant (GT) and 15 lean, GT volu...
430 Citations Source Cite
Published on Mar 1, 2004in Diabetes Care 13.40
John C. Pickup49
Estimated H-index: 49
There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properti...
926 Citations Source Cite
Cited By1
Peter M. Abadir9
Estimated H-index: 9
(Johns Hopkins University),
Helmy M. Siragy36
Estimated H-index: 36
(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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