Role of neuroinflammation in hypertension-induced brain amyloid pathology

Carnevale, Daniela; Mascio, Giada; Ajmone‐Cat, Maria Antonietta; D’Andrea, Ivana; Cifelli, Giuseppe; Madonna, Michele; Cocozza, Germana; Frati, Alessandro; Carullo, Pierluigi; Carnevale, Lorenzo; Alleva, Enrico; Branchi, Igor; Lembo, Giuseppe; Minghetti, Luisa

doi:10.1016/j.neurobiolaging.2010.08.013

Cited by 87 publications

(68 citation statements)

References 27 publications

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“…15,25,28 Using transverse aortic constriction and angiotensin II infusion, cerebral amyloid deposition was observed as early as 4 weeks after the insult in both models. 15 They observed an increased permeability of the blood-brain barrier with albumin leakage in the cortex. In several brain areas controlling cognitive functions, such as the cortex, soluble oligomers and intermediate amyloids were recognized.…”

Section: Discussionmentioning

confidence: 99%

“…16 For detection of chronotropic activity of various Aβ peptides, Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), Aβ (10-35), Aβ , and Aβ (1-42) obtained from antibodies-online were added to neonatal rat cardiomyocytes at a concentration of 0.1 µmol/L. To show activation of a G-protein-coupled receptor and identify the receptor, β 1 (bisoprolol, 1 µmol/L) and β 2 (ICI 118.551, 0.1 µmol/L) adrenergic receptor antagonist, angiotensin II receptor type 1 (AT 1 ) receptor blocker, 1 µmol/L irbesartan, α 1A -AR blockers, 1 µmol/L prazosin, and 1 µmol/L urapidil were added.…”

Section: Cardiac Contraction Assay Preparation Of Human α 1 -Ar Antimentioning

confidence: 99%

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Amyloid-β Peptides Activate α ₁ -Adrenergic Cardiovascular Receptors

et al. 2013

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A lzheimer disease (AD) features the accumulation of amyloid-β (Aβ) in neuritic plaques, brain parenchyma, and walls of cerebral vessels.1,2 Aβ peptides are the cleavage products of the transmembrane amyloid precursor protein and are naturally produced within the central nervous system throughout life.3 Aβ are degraded, chemically modified, and cross-linked, thereby increasing their relative insolubility, stability, and toxicity. 4 Aβ peptides from amyloid deposits in brain and cerebrospinal fluid vary in amino acid composition, ranging from the full-length Aβ (1-40) and Aβ (1-42) peptides to shorter carboxy-terminal Aβ peptides, as well as aminoterminal truncated species. 5 The ability to affect cognitive processes is typical not only of the full-length peptide but also of several Aβ fragments, in particular the undecapeptide Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). 6,7 The fragment consists of amino acid residues 25 to 35 in Aβ (GSNKGAIIGLM) that can form large β-pleated sheet fibrils similar to those obtained by full-length Aβ. Aβ (25-35) exhibits a potent vasoconstrictor effect in rat skin microvasculature and elicits endothelial dysfunction.8 Aβ (25-35) also induces interleukin 1β release from macrophages and microglia. 9 AD may be aggravated by vascular mechanisms.10,11 Aβ peptides can enhance vasoconstriction when deposited in microvessels, 12 and cause abnormal vascular reactivity even without vascular deposition. 13,14 Epidemiological data associate hypertension with AD.14 In preliminary observations, we observed that several Aβ peptides influence the spontaneously beating rate of neonatal rat cardiomyocytes 15 in a fashion similar to autoantibodies we described earlier that stimulate the α 1 -adrenergic receptor (α 1 -AR) in patients with refractory hypertension. 16 Furthermore, Karczewski et al 17 used MRI and observed a pathological role of α 1 -AR in the brain vasculature. These observations caused us to pursue the mechanisms by which Aβ influences cardiovascular cells.Abstract -Alzheimer disease features amyloid-β (Aβ) peptide deposition in brain and blood vessels and is associated with hypertension. Aβ peptide can cause vasoconstriction and endothelial dysfunction. We observed that Aβ peptides exert a chronotropic effect in neonatal cardiomyocytes, similar to α 1 -adrenergic receptor autoantibodies that we described earlier.Recently, it was shown that α 1 -adrenergic receptor could impair blood-brain flow. We hypothesized that Aβ peptides might elicit a signal transduction pathway in vascular cells, induced by α 1 -adrenergic receptor activation. Aβ (25-35) and Aβ

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Section: Discussionmentioning

confidence: 99%

Section: Cardiac Contraction Assay Preparation Of Human α 1 -Ar Antimentioning

confidence: 99%

Amyloid-β Peptides Activate α ₁ -Adrenergic Cardiovascular Receptors

et al. 2013

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“…Epidemiological studies provide evidence that in addition to the increased prevalence of hypertension in aging, the deleterious cerebrovascular effects of hypertension are also exacerbated in elderly patients, whereas younger subjects appear to be more protected from cerebromicrovascular and neurological damage induced by elevated blood pressure (10,38,54). There is strong evidence showing that in older patients hypertensioninduced microvascular injury not only promotes the development of vascular cognitive impairment (24,29,45) but it also significantly increases the risk (risk ratio ϭ ϳ1.5) for sporadic Alzheimer's disease (25,31), supporting the vascular hypothesis of the disease (11)(12)(13). Although the available human data suggest that advanced age and hypertension have synergistic effects (45), the specific age-related mechanisms through which aging increases the vulnerability of the cerebromicrovasculature to hypertension are not well documented in the literature.…”

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confidence: 90%

Role of 20-HETE, TRPC channels, and BK_Ca in dysregulation of pressure-induced Ca²⁺ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice

Tóth

Csiszár

Tucsek

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

100

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Toth P, Csiszar A, Tucsek Z, Sosnowska D, Gautam T, Koller A, Schwartzman ML, Sonntag WE, Ungvari Z. Role of 20-HETE, TRPC channels, and BK Ca in dysregulation of pressure-induced Ca 2ϩ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice. Am J Physiol Heart Circ Physiol 305: H1698 -H1708, 2013. First published October 4, 2013; doi:10.1152/ajpheart.00377.2013.-Hypertension in the elderly substantially increases the risk of stroke and vascular cognitive impairment in part due to an impaired functional adaptation of aged cerebral arteries to high blood pressure. To elucidate the mechanisms underlying impaired autoregulatory protection in aging, hypertension was induced in young (3 mo) and aged (24 mo) C57BL/6 mice by chronic infusion of angiotensin II and pressureinduced changes in smooth muscle cell (SMC) intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) and myogenic constriction of middle cerebral arteries (MCA) were assessed. In MCAs from young hypertensive mice, pressure-induced increases in vascular SMC [Ca 2ϩ ]i and myogenic tone were increased, and these adaptive responses were inhibited by the cytochrome P-450 -hydroxylase inhibitor HET0016 and the transient receptor potential (TRP) channel blocker SKF96365. Administration of 20-hydroxyeicosatetraenoic acid (HETE) increased SMC [Ca 2ϩ ]i and constricted MCAs, and these responses were inhibited by SKF96365. MCAs from aged hypertensive mice did not show adaptive increases in pressure-induced calcium signal and myogenic tone and responses to HET0016 and SKF96365 were blunted. Inhibition of large-conductance Ca 2ϩ -activated K ϩ (BK) channels by iberiotoxin enhanced SMC [Ca 2ϩ ]i and myogenic constriction in MCAs of young normotensive animals, whereas it was without effect in MCAs of young hypertensive mice. Iberiotoxin did not restore myogenic adaptation in MCAs of aged hypertensive mice. Thus functional maladaptation of aged cerebral arteries to hypertension is due to the dysregulation of pressure-induced 20-HETE and TRP channel-mediated SMC calcium signaling, whereas overactivation of BK channels is unlikely to play a role in this phenomenon.cerebral blood flow; 20-hydroxyeicosatetraenoic acid; autoregulation; canonical transient receptor potential; potassium channels; largeconductance Ca 2ϩ -activated K ϩ channels THERE IS GROWING EVIDENCE that hypertension, which affects ϳ50 million Americans, exerts deleterious effects on the cerebral circulation and thereby causes accelerated brain aging (45). The elderly (Ն65 years of age), representing the fastestgrowing segment of the US population, have the highest prevalence of hypertension, and these individuals are more likely to develop cerebrovascular pathologies (5). Epidemiological studies provide evidence that in addition to the increased prevalence of hypertension in aging, the deleterious cerebrovascular effects of hypertension are also exacerbated in elderly patients, whereas younger subjects appear to be more protected from cerebromicrovascular and neurological damage in...

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“…37 These findings should be interpreted in the knowledge that such biomarkers may also be increased in patients with more general cardiovascular disease. In general, the functional consequences of neuroinflammation are currently unclear, 43 particularly in relation to CABG surgery and POCD.…”

Section: Hogan Et Al Fixing Hearts and Protecting Minds 163mentioning

confidence: 99%