(Pro)renin receptors and angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor axis in human aortic valve stenosis

Peltonen, T; Näpänkangas, Juha; Ohtonen, Pasi; Aro, Jani; Peltonen, Jenni; Soini, Ylermi; Juvonen, Tatu; Satta, Jari; Ruskoaho, Heikki; Taskinen, Panu

doi:10.1016/j.atherosclerosis.2011.01.018

Cited by 30 publications

(21 citation statements)

References 31 publications

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“…Aortic valve calcification and vascular density were higher in the AS and AR+f groups than in the control or AR groups, as we have shown before [13], [25], [26]. In the control group, no lymphatic vessels were found, as expected (Fig.1A).…”

Section: Valve Calcification Vascular Density Lymphatic Vessel Counsupporting

confidence: 82%

Increased mesenchymal podoplanin expression is associated with calcification in aortic valves

Näpänkangas

Ohtonen

Ohukainen

et al. 2019

Cardiovascular Pathology

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Section: Valve Calcification Vascular Density Lymphatic Vessel Counsupporting

confidence: 82%

Increased mesenchymal podoplanin expression is associated with calcification in aortic valves

Näpänkangas

Ohtonen

Ohukainen

et al. 2019

Cardiovascular Pathology

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“…These results raise the theory that activation of the ACE2/Ang-(1-7)/Mas axis may prove to be a novel therapeutic target for other diseases where the underlying pathology involves inflammation, such as other cardiovascular diseases, type 2 diabetes, chronic kidney disease, and cancer (Manabe, 2011). There is accumulating evidence that the activation of this axis has anti-inflammatory effects in many tissues, including the heart (Giani et al, 2010), aortic valve (Peltonen et al, 2011) and kidneys (Giani et al, 2011). Since we demonstrate a central effect here, it also may prove to have therapeutic potential for other brain diseases that involve inflammation, such as Alzheimer's disease (Manabe, 2011).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of angiotensin-(1-7) in ischemic stroke

et al. 2013

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Previously we demonstrated that central administration of angiotensin-(1-7) [Ang-(1-7)] into rats elicits significant cerebroprotection against ischemic stroke elicited by endothelin-1 induced middle cerebral artery occlusion. Ang-(1-7), acting via its receptor Mas, reduced cerebral infarct size, and rats exhibited improved performance on neurological exams. These beneficial actions of Ang-(1-7) were not due to inhibition of the effects of endothelin-1 on cerebral vasoconstriction or effects on cerebral blood flow, and so we considered other potential mechanisms. Here we investigated the possibility that the Ang-(1-7)-induced cerebroprotection involves an anti-inflammatory effect, since stroke-induced cerebral damage includes an excessive intracerebral inflammatory response. Our quantitative RT-PCR analyses revealed that central Ang-(1-7) treatment attenuates the increased expression of mRNAs for inducible nitric oxide synthase (iNOS), several pro-inflammatory cytokines and cluster of differentiation molecule 11b (microglial marker) within the cerebral cortex following endothelin-1 induced stroke. Western blotting confirmed similar changes in iNOS protein expression in the cerebral cortex. In support of these observations, immunostaining revealed the presence of immunoreactive Mas on activated microglia within the cerebral cortical infarct zone, and in vitro experiments demonstrated that lipopolysaccharide-induced increases in nitric oxide production in glial cultures are attenuated by Ang-(1-7) acting via Mas. Collectively these findings demonstrate an anti-inflammatory action of Ang-(1-7) in the brain, and suggest that the cerebroprotective action of this peptide in ischemic stroke may involve effects on nitric oxide generation by microglia.

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“…Although angiotensin II is also able to mediate antifibrotic and antiinflammatory effects via angiotensin II type 2 (AT 2 ) receptors, differential expression of these receptors in favor of AT 1 has been demonstrated in calcified aortic valves, so that a profibrotic profile dominates. Likewise, although angiotensinconverting enzyme type 2 (ACE-2) exerts antifibrotic and anti-inflammatory influences via the Ang1-7/Mas pathway, this pathway is down-regulated in calcified aortic stenosis, with reduced expression of both ACE-2 and Mas receptors in calcified valves compared with control subjects (26). Increased RAS expression is, therefore, implicated in the development of fibrosis within the valve.…”

Section: Calcification In Aortic Stenosismentioning

confidence: 99%

Calcification in Aortic Stenosis

Pawade

Newby

Dweck³

2015

Journal of the American College of Cardiology

310

258

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Aortic stenosis is a common, potentially fatal condition that is set to become an increasing public health burden. Once symptoms develop, there is an inexorable deterioration with a poor prognosis. Despite this, there are no medical therapies capable of modifying disease progression, and the only available treatment is aortic valve replacement, to which not all patients are suited. Conventional teaching suggests that aortic stenosis is a degenerative condition whereby "wear and tear" leads to calcium deposition within the valve. Although mechanical stress and injury are important factors, it is becoming increasingly appreciated that aortic stenosis is instead governed by a highly complex, regulated pathological process with similarities to skeletal bone formation. This review discusses the pathophysiology of aortic stenosis with an emphasis on the emerging importance of calcification, how this can be visualized and monitored using noninvasive imaging, and how our improved knowledge may ultimately translate into novel disease-modifying treatments. (J Am Coll Cardiol 2015;66:561-77)

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(Pro)renin receptors and angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor axis in human aortic valve stenosis

Cited by 30 publications

References 31 publications

Increased mesenchymal podoplanin expression is associated with calcification in aortic valves

Increased mesenchymal podoplanin expression is associated with calcification in aortic valves

Anti-inflammatory effects of angiotensin-(1-7) in ischemic stroke

Calcification in Aortic Stenosis

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