Article

Augmentation of the renin-angiotensin system by hypercholesterolemia promotes vascular diseases.

University of Kentucky, Wethington Building, Room 521, Lexington, KY 40536-40200, USA, Tel.: +1 859 323 4933 ext. 81389, , .
Future Lipidology (Impact Factor: 1.08). 12/2008; 3(6):625-636. DOI: 10.2217/17460875.3.6.625
Source: PubMed

ABSTRACT Activation of the renin-angiotensin system (RAS) and aberrant cholesterol metabolism have generally been considered as independent mechanisms in the development of several vascular diseases. However, it is becoming increasingly apparent in both human and animal studies that many aspects of the RAS may be augmented by hypercholesterolemia, resulting in enhancement of the severity and occurrence of several vascular diseases, including hypertension, atherosclerosis and abdominal aortic aneurysms. Some potential hypercholesterolemia-induced mechanisms have been demonstrated to increase activity of specific components of the RAS. These include increased AT1-receptor expression, increased responsiveness to Ang II and increased synthesis of angiotensin peptides. Future studies need to validate mechanisms of hypercholesterolemia-induced RAS activation in different vascular diseases.

Download full-text

Full-text

Available from: Alan Daugherty, Jul 03, 2015
0 Followers
 · 
120 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The renin angiotensin system (RAS) has profound effects on atherosclerosis development in animal models, which is partially complimented by evidence in the human disease. Although angiotensin II was considered to be the principal effector of the RAS, a broader array of bioactive angiotensin peptides have been identified that have increased the scope of enzymes and receptors in the RAS. Genetic interruption of the synthesis of these peptides has not been extensively performed in experimental or human studies. A few studies demonstrate that interruption of a component of the angiotensin peptide synthesis pathway reduces experimental lesion formation. The evidence in human studies has not been consistent. Conversely, genetic manipulation of the RAS receptors has demonstrated that AT1a receptors are profoundly involved in experimental atherosclerosis. Few studies have reported links of genetic variants of angiotensin II receptors to human atherosclerotic diseases. Further genetic studies are needed to define the role of RAS in atherosclerosis.
    Current Atherosclerosis Reports 05/2010; 12(3):167-73. DOI:10.1007/s11883-010-0109-4 · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: The objective of this paper is to investigate a profile on circulatory renin-angiotensin system (RAS) activity in hypercholesterolemic (HC) patients treated with statins. METHODS: Eighteen primary HC patients and 18 sex- and age-matched healthy adults were included in this study as controls. Total cholesterol (TC), triglyceride (TG), LDL-C, blood glucose, angiotensin-converting enzyme (ACE) activity, and angiotensin II (Ang II) levels were measured before and four and eight weeks after beginning statin treatment in the HC group. Similar measurements were taken in the control group at baseline. RESULTS: At baseline, TC, TG and LDL-C levels, as well as ACE activity and Ang II concentrations, were significantly higher in the HC group than in the control group. Based on the baseline data collection of 36 participants, there were significant positive correlations between ACE activity and TC (r = 0.54) or LDL-C (r = 0.51), and between Ang II level and TC (r = 0.34) or LDL-C (r = 0.27). TC, LDL-C, Ang II (35.46±14.49 vs 71.10±20.47 pg/ml, p < 0.05) levels and ACE activity (108.9±51.9 vs 180.1±71.3 U/L, p < 0.05) were decreased in HC patients eight weeks after starting statin treatment. In HC patients, RAS activity correlated positively with TC and LDL-C levels before and after treatment. CONCLUSIONS: In HC patients, lowering serum cholesterol with statins is associated with decreased circulatory RAS activity.
    Journal of Renin-Angiotensin-Aldosterone System 03/2013; 16(1). DOI:10.1177/1470320313483349 · 2.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Angiotensin II (angII) accelerates atherosclerosis, but the mechanisms are not fully understood. The aim of this study was to determine whether TGFβ is required for angII-induced atherosclerosis. Ldlr null mice fed a normal chow diet were infused with angII or saline for 28 days. A single injection of TGFβ neutralizing antibody 1D11 (2mg/kg) prevented angII- induction of TGFβ1 levels, and strikingly attenuated angII-induced accumulation of aortic biglycan content. To study atherosclerosis, mice were infused with angII or saline for 4 weeks, then fed Western diet for a further 6 weeks. 1D11 had no effect on systolic blood pressure or plasma cholesterol; however, angII-infused mice that received 1D11 had reduced atherosclerotic lesion area by 30% (p<0.05). Immunohistochemical analyses demonstrated that angII induced both lipid retention and accumulation of biglycan and perlecan which co-localized with apoB. 1D11 strikingly reduced the effect of angII on biglycan but not perlecan. 1D11 decreased total collagen content (p<0.05) in lesion area without changing plaque inflammation markers (CD68 and CD45). Thus, this study demonstrates that neutralization of TGFβ attenuated angII stimulation of biglycan accumulation and atherogenesis in mice, suggesting that TGFβ-mediated biglycan induction is one of the mechanisms underlying angII-promoted atherosclerosis.
    The Journal of Lipid Research 06/2013; DOI:10.1194/jlr.P040139 · 4.73 Impact Factor