Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition

Goel, Ruby; Bhat, Shahnawaz Ali; Rajasekar, N.; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

doi:10.1016/j.pbb.2015.04.002

Cited by 40 publications

(41 citation statements)

References 48 publications

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“…The use of perindopril, a potent ACEI, in combating neuro-cognition associated pathologies is reported and supported by Perindopril Protection Against Recurrent Stroke Study (Tzourio et al, 2003). Interestingly, oral administration of perindopril in SHRs improved memory and reduced neurodegeneration by lowering NF-kB pathway, possibly by lowering the level of ang II (Goel et al, 2015). A similar antiinflammatory effect was observed in 5X familial AD mice after intranasal application of telmisartan [ARB] and perindopril [ACEI] (Torika et al, 2016).…”

Section: Neuro-inflammationmentioning

confidence: 76%

“…They reported that the blockade of the Ang II/AT1R axis and upregulation of peroxisome proliferator-activated receptor gamma might reduce inflammation by modulating neurotrophic factors (NFs) that activate neuroprotective pathways (Wang et al, 2014;Sathiya et al, 2013;Tong et al, 2016). In addition, telmisartan was found to attenuate lipopolysaccharide induced NO, TNF-a, interleukin 1 beta (IL1-b) as a possible novel neuroprotective mechanism, reinforcing the hypothesis that brain RAS may regulate memory via neuroinflammation (Montgomery et al, 2012, Nakamura andLipton, 2011;Goel et al, 2015).…”

Section: Neuro-inflammationmentioning

confidence: 86%

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Role of brain renin angiotensin system in neurodegeneration: An update

Abiodun¹,

Ola²

2020

Saudi Journal of Biological Sciences

115

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a b s t r a c tRenin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1-7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1-7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.

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Section: Neuro-inflammationmentioning

confidence: 76%

Section: Neuro-inflammationmentioning

confidence: 86%

Role of brain renin angiotensin system in neurodegeneration: An update

Abiodun¹,

Ola²

2020

Saudi Journal of Biological Sciences

115

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“…112 rats were randomly divided into six groups: (a) naïve, n = 14; (b) scramble siRNA, n = 16; (c) LPS (Sigma‐Aldrich, St. Louis, MO, USA, 12.5 μg of LPS dissolved in 50 nL of saline), n = 17; (d) LPS+rSAP130 (Abnova, Taiwan, China, 25 ng in 50 nL of saline), n = 21; (e) LPS+rSAP130 + NLRP3 siRNA (Thermo Fisher, 250 pmol/50 nL), n = 22; (f) LPS+rSAP130 + gevokizumab (XOMA 052; XOMA Corporation, Emeryville, CA, USA, 50 nL of saline solution containing 10 μg of gevokizumab), n = 22. The doses of reagents were referred according to previous studies . Animals in naïve group did not receive any procedure except anesthesia until RSNA measurement.…”

Section: Methodsmentioning

confidence: 99%

Microglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat

Wang

Yin

Wang

et al. 2018

J Cellular Molecular Medi

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Malignant ventricular arrhythmias (VAs) following myocardial infarction (MI) is a lethal complication resulting from sympathetic nerve hyperactivity. Numerous evidence have shown that inflammation within the paraventricular nucleus (PVN) participates in sympathetic hyperactivity. Our aim was to explore the role of Macrophage‐inducible C‐type lectin (Mincle) within the PVN in augmenting sympathetic activity following MI,and whether NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome/IL‐1β axis is involved in this activity. MI was induced by coronary artery ligation. Mincle expression localized in microglia within the PVN was markedly increased at 24 hours post‐MI together with sympathetic hyperactivity, as indicated by measurement of the renal sympathetic nerve activity (RSNA) and norepinephrine (NE) concentration. Mincle‐specific siRNA was administrated locally to the PVN, which consequently decreased microglial activation and sympathetic nerve activity. The MI rats exhibited a higher arrhythmia score after programmed electric stimulation than that treated with Mincle siRNA, suggesting that the inhibition of Mincle attenuated foetal ventricular arrhythmias post‐MI. The underlying mechanism of Mincle in sympathetic hyperactivity was investigated in lipopolysaccharide (LPS)‐primed naïve rats. Recombinant Sin3A‐associated protein 130kD (rSAP130), an endogenous ligand for Mincle, induced high levels of NLRP3 and mature IL‐1β protein. PVN‐targeted injection of NLRP3 siRNA or IL‐1β antagonist gevokizumab attenuated sympathetic hyperactivity. Together, the data indicated that the knockdown of Mincle in microglia within the PVN prevents VAs by attenuating sympathetic hyperactivity and ventricular susceptibility, in part by inhibiting its downstream NLRP3/IL‐1β axis following MI. Therapeutic interventions targeting Mincle signalling pathway could constitute a novel approach for preventing infarction injury.

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“…The methodology of the 19 animal studies varied widely in the selection of animals and drugs used, length of treatment times, and outcomes. Animal models ranged from mouse models using wild-type mice [ 13 , 23 ], aged Swiss mice [ 31 ], wild-type mice treated with icv amyloid beta 25–35 to be used as an AD mouse model [ 27 ], and transgenic (Tg) AD mice alone [ 17 , 19 , 21 , 29 , 30 ], to rat models such as Wistar [ 18 , 20 ], Sprague-Dawley [ 16 , 22 ], or spontaneously hypertensive rats (SHR) [ 14 , 15 , 24 , 26 , 28 ]. Regarding AHM used, 17 of the 19 studies used CCB, ACE-I, or ARB alone or in combination.…”

Section: Resultsmentioning

confidence: 99%

“…Regarding AHM used, 17 of the 19 studies used CCB, ACE-I, or ARB alone or in combination. Commercially available ACE-Is used were captopril [ 17 , 18 , 29 ], enalapril [ 27 ], imidapril [ 27 ], lisinopril [ 14 ], perindopril [ 26 , 27 ], and trandolapril [ 19 ]. ARBs used included losartan [ 18 , 19 , 25 ], olmesartan [ 24 ], telmisartan [ 15 , 22 , 28 ], and valsartan [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Antihypertensive Medications and Cognitive Impairment: Part II. Review of Physiology and Animal Studies

et al. 2016

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Purpose of ReviewThere is an established association between hypertension and increased risk of poor cognitive performance and dementia including Alzheimer’s disease; however, associations between antihypertensive medications (AHM) and dementia risk are less clear. An increased interest in AHM has resulted in expanding publications; however, none of the recent reviews provide comprehensive review. Our extensive review includes 24 mechanistic animal and human studies published over the last 5 years assessing relationship between AHM and cognitive function.Recent FindingsAll classes of AHM showed similar result patterns in animal studies. The mechanism by which AHM exert their effect was extensively studied by evaluating well-established pathways of AD disease process, including amyloid beta (Aβ), vascular, oxidative stress and inflammation pathways, but only few studies evaluated the blood pressure lowering effect on the AD disease process.SummaryMethodological limitations of the studies prevent comprehensive conclusions prior to further work evaluating AHM in animals and larger human observational studies, and selecting those with promising results for future RCTs.

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Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition

Cited by 40 publications

References 48 publications

Role of brain renin angiotensin system in neurodegeneration: An update

Role of brain renin angiotensin system in neurodegeneration: An update

Microglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat

Relationship Between Antihypertensive Medications and Cognitive Impairment: Part II. Review of Physiology and Animal Studies

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