Alzheimer's, Angiotensin IV and an Aminopeptidase

Albiston, Anthony L.; Fernando, Ruani; Ye, Siying; Peck, Grantley R.; Chai, Siew Yeen

doi:10.1248/bpb.27.765

Cited by 36 publications

(26 citation statements)

References 31 publications

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“…The robust effect of AngIV in enhancement of learning and memory has pointed to IRAP as a novel potential pharmacological target for dementia [41]. The present study extends these perspectives toward neuroprotection in cerebral ischemia.…”

Section: Discussionsupporting

confidence: 57%

Protective effect of candesartan in experimental ischemic stroke in the rat mediated by AT2 and AT4 receptors

Faure

Bureau

Oudart

et al. 2008

Journal of Hypertension

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Section: Discussionsupporting

confidence: 57%

Protective effect of candesartan in experimental ischemic stroke in the rat mediated by AT2 and AT4 receptors

Faure

Bureau

Oudart

et al. 2008

Journal of Hypertension

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“…Central administration of Ang IV or LVV-hemorphin 7 not only markedly enhances learning and memory in normal rodents, but also reverses memory deficits observed in animal models of amnesia (Albiston et al 2004a).…”

Section: Angiotensins and Neurological Disordersmentioning

confidence: 92%

The CNS renin-angiotensin system

2006

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The renin-angiotensin system (RAS) is one of the best-studied enzyme-neuropeptide systems in the brain and can serve as a model for the action of peptides on neuronal function in general. It is now well established that the brain has its own intrinsic RAS with all its components present in the central nervous system. The RAS generates a family of bioactive angiotensin peptides with variable biological and neurobiological activities. These include angiotensin-(1-8) [Ang II], angiotensin-(3-8) [Ang IV], and angiotensin-(1-7) [Ang-(1-7)]. These neuroactive forms of angiotensin act through specific receptors. Only Ang II acts through two different high-specific receptors, termed AT1 and AT2. Neuronal AT1 receptors mediate the stimulatory actions of Ang II on blood pressure, water and salt intake, and the secretion of vasopressin. In contrast, neuronal AT2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic to AT1 receptors. Among the many potential effects mediated by stimulation of AT2 are neuronal regeneration after injury and the inhibition of pathological growth. Ang-(1-7) mediates its antihypertensive effects by stimulating the synthesis and release of vasodilator prostaglandins and nitric oxide and by potentiating the hypotensive effects of bradykinin. New data concerning the roles of Ang IV and Ang-(1-7) in cognition also support the existence of complex site-specific interactions between multiple angiotensins and multiple receptors in the mediation of important central functions of the RAS. Thus, the RAS of the brain is involved not only in the regulation of blood pressure, but also in the modulation of multiple additional functions in the brain, including processes of sensory information, learning, and memory, and the regulation of emotional responses.

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“…Whether LVV-H7 may be used for evaluation of thrombus-associated aneurysmal progression in AAA would need further investigation. However, the half-life of small peptides in the circulation depends on several factors, such as their elimination rate in urine and their trapping by potential receptors (ie, angiotensin receptors in brain 24 or opioid receptors 18 ).…”

Section: Dejouvencel Et Al Hemoglobin Proteolysis In Aaa 273mentioning

confidence: 99%

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

Dejouvencel

Feron

Rossignol

et al. 2010

ATVB

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Objective-In human abdominal aortic aneurysm, the accumulation of blood-derived cells and proteases within the mural thrombus plays a pivotal role in the evolution toward vessel wall rupture. We sought to identify peptides released from abdominal aortic aneurysm specimens, characterized by an intraluminal thrombus. Methods and Results-Intraluminal thrombus samples were analyzed by differential proteomics, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A 1309-Da peptide was detected in larger amounts in the newly formed luminal thrombus layer relative to older layers. It was identified as being LVVYPWTQRF (known as LVV-Hemorphin 7), a peptide generated from hemoglobin by cathepsin D. By immunohistochemical analysis, we showed that Hemorphin 7 (H7) colocalizes with cathepsin D and cathepsin G in the luminal layer of the intraluminal thrombus. In vitro, cathepsin G was able to generate H7 peptides at pH 7.4, whereas cathepsin D was only active in acidic conditions. Finally, H7 peptides were shown to be increased 3-to 4-fold in sera of abdominal aortic aneurysm patients relative to controls, and their levels were positively correlated with the volume of the thrombus. Key Words: Human atherothrombosis Ⅲ cathepsin G Ⅲ cathepsin D Ⅲ circulating biomarker Ⅲ thrombus I n human atherothrombosis, the accumulation of bloodderived cells and zymogens contributes to oxidation and proteolysis, together leading to arterial wall destabilization. 1 Depending on the arterial territory, complications associated with atherosclerosis may evolve toward stenosis, frequent in carotid, coronary, and femoral arteries, or outward remodeling, mainly in the aorta. In abdominal aorta, where atherothrombosis frequently develops, evolution toward aneurysm is characterized by the presence of a dynamic intraluminal mural thrombus (ILT), which represents a source of blood-borne proteases participating in extracellular matrix degradation and smooth muscle cell apoptosis, preventing thrombus colonization and cicatrization. 2,3 In the present study, we aimed to look for biomarkers reflecting the pathological remodeling of aortic atherothrombosis associated with the thrombus in abdominal aortic aneurysm (AAA). For this purpose, we used a differential proteomics approach comparing the different layers of human AAA samples, including the thrombus, and the remaining media. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), a particularly well-suited technology for detection of peptides and small proteins, including proteolytic fragments. Our hypothesis is that the proteases conveyed by leukocytes (matrix metalloproteases, elastase, cathepsins, etc) or those generated in situ (ie, plasmin, thrombin) may produce protein fragments reflecting the pathological vascular remodeling. 4 Our strategy was thus to compare the profiles of low-molecular-weight proteins and peptides released by AAA samples. Such peptides could be used as biomarkers of the thrombus activity and an...

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Alzheimer's, Angiotensin IV and an Aminopeptidase

Cited by 36 publications

References 31 publications

Protective effect of candesartan in experimental ischemic stroke in the rat mediated by AT2 and AT4 receptors

Protective effect of candesartan in experimental ischemic stroke in the rat mediated by AT2 and AT4 receptors

The CNS renin-angiotensin system

Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm

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