Endothelial Damage and Regeneration: The Role of the Renin-Angiotensin-Aldosterone System

Becher, Ulrich; Endtmann, Cathleen; Tiyerili, Vedat; Nickenig, Georg; Werner, Nikos

doi:10.1007/s11906-010-0171-x

Cited by 46 publications

(28 citation statements)

References 55 publications

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“…It has been suggested that AngII-induced mesangial cell contraction with efferent arteriolar vasoconstriction initiates intraglomerular hypertension and may lead to enhanced matrix formation and renal fibrosis after increased synthesis of TGF-β 50 . Several studies have shown that angiotensin II type 1 receptor blockers (ARBs), are particularly effective to reduce proteinuria through their direct action on AT1R-expressing cells in endothelium and vascular smooth muscle expressing the receptor 51, 52 . Therefore blocking the renin-angiotensin-aldosterone system would be beneficial beyond its effect on blood pressure 52 .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that angiotensin II type 1 receptor blockers (ARBs), are particularly effective to reduce proteinuria through their direct action on AT1R-expressing cells in endothelium and vascular smooth muscle expressing the receptor 51, 52 . Therefore blocking the renin-angiotensin-aldosterone system would be beneficial beyond its effect on blood pressure 52 . For example, the glomerular efferent arteriole is particularly sensitive to angiotensin II 53 .…”

Section: Discussionmentioning

confidence: 99%

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The IgA1 immune complex–mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

Tamouza

Chemouny

Kafková

et al. 2012

Kidney International

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IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and has significant morbidity and mortality as 20–40% of patients progress to end-stage renal disease (ESRD) within 20 years after disease onset. We aimed to gain insight into the molecular mechanisms involved in IgAN progression. A systematic evaluation of renal biopsy specimens from IgAN patients revealed that the MAPK/ERK signaling pathway was activated in mesangial areas of patients presenting with >1 g/day proteinuria and elevated blood pressure, but was absent in biopsy specimens from IgAN patients with modest proteinuria (<1 g/day). ERK activation was not associated with elevated serum levels of galactose (Gal)-deficient IgA1 or IgG specific for Gal-deficient IgA1. In in vitro studies with human mesangial cells, ERK activation controlled pro-inflammatory cytokine secretion and was induced by patients’ large-molecular-mass IgA1-containing circulating immune complexes. Moreover, we show that IgA1-dependent MAPK/ERK activation required renin-angiotensin system (RAS) activity. Finally, RAS blockers were more efficient in reducing proteinuria in IgAN patients exhibiting substantial mesangial activation of MAPK/ERK. Together, these results suggest that MAPK/ERK activation alters the mesangial cell-podocyte cross-talk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation status in diagnostic renal biopsies could therefore serve as a biomarker to predict the efficacy of RAS blockers in IgAN.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The IgA1 immune complex–mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

Tamouza

Chemouny

Kafková

et al. 2012

Kidney International

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“…Although a vasoconstrictor, Ang II induces endothelial damage by inhibiting endothelial cells regeneration. Ang II acts as a second messenger to activate intracellular signaling pathways such as mitogen-activated protein kinase (MAPK) and AKT, pathways that mediate cell proliferation and apoptosis and thereby vascular dysfunction [51]. Ang II plays a significant role in the initiation and progression of atherogenesis, an inflammation mediated process.…”

Section: Raas and Vascular Inflammationmentioning

confidence: 99%

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

Pacurari

Kafoury

Tchounwou

et al. 2014

International Journal of Inflammation

301

230

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The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

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“…These include: Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), Transforming Growth Factor beta (TGF-β) and Insulin-like Growth Factor 1 (IGF-1) g and may contribute to the tissue fibrogenesis properties of the RAS [12]. Activation of NADPH oxidase pathway and stimulation of ROS production in different cell types is another major downstream of AT1 stimulation [5].…”

Section: The Classical Ras Axis Of Regulationmentioning

confidence: 99%

Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention

Ahmadian

Pennefather

Eftekhari

et al. 2016

Expert Review of Gastroenterology & Hepatology

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The current review aimed to outline the functions of the renin angiotensin system (RAS) in the context of the oxidative stress-associated liver disease. Areas covered: Angiotensin II (Ang II) as the major effector peptide of the RAS is a pro-oxidant and fibrogenic cytokine. Mechanistically, NADPH oxidase (NOX) is a multicomponent enzyme complex that is able to generate reactive oxygen species (ROS) as a downstream signaling pathway of Ang II which is expressed in liver. Ang II has a detrimental role in the pathogenesis of chronic liver disease through possessing pro-oxidant, fibrogenic, and pro-inflammatory impact in the liver. The alternative axis (ACE2/Ang(1-7)/mas) of the RAS serves as an anti-inflammatory, antioxidant and anti-fibrotic component of the RAS. Expert commentary: In summary, the use of alternative axis inhibitors accompanying with ACE2/ Ang(1-7)/mas axis activation is a promising new strategy serving as a novel therapeutic option to prevent and treat chronic liver diseases.

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Endothelial Damage and Regeneration: The Role of the Renin-Angiotensin-Aldosterone System

Cited by 46 publications

References 55 publications

The IgA1 immune complex–mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

The IgA1 immune complex–mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

Role of renin-angiotensin system in liver diseases: an outline on the potential therapeutic points of intervention

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