Attenuated atherogenesis in apolipoprotein E-deficient mice lacking amyloid precursor protein

Parre, Tim J.L. Van De; Guns, Pieter-Jan; Fransen, Paul; Martinet, Wim; Bult, Hidde; Herman, Arnold G.; Meyer, Guido R.Y. De

doi:10.1016/j.atherosclerosis.2011.01.032

Cited by 23 publications

(23 citation statements)

References 18 publications

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“…Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) increased the beating rate of neonatal rat cardiomyocytes in a time-dependent manner, whereas the negative control peptide with a reverse sequence of Aβ (25-35) did not change the frequency of spontaneously beating neonatal cardiomyocytes ( Figure 1A). We found that the beating rate increased ≤4 hours (P≤0.005).…”

Section: Resultsmentioning

confidence: 99%

“…This staining could be blocked by urapidil. Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and Aβ (10-35) induced strong α 1A -AR staining that was also blocked by urapidil. None of the other Aβ peptides led to receptor activation (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…The chronotropic effect of Aβ (25-35) was blocked by prazosin and urapidil, whereas β 1 and β 2 adrenergic receptor antagonists and angiotensin II AT 1 receptor blocker had no effect ( Figure 1B). Dose-response curves of Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) were generated (10 −6 to 10 −10 mol/L) in one log order concentrations and showed a typical sigmoid curve ( Figure 1C to α 1 -AR, we used synthetic peptides corresponding to the sequence of the first extracellular loop (P37, P38, P39), and the second extracellular loop (P40) of the human α 1 Α-AR (Figure 2A). Epitope α 1A -AR mapping by cardiac contraction assay was performed with overlapping peptide sequences ( Figure 2B).…”

Section: Resultsmentioning

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%

“…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.…”

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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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