Table 2.

Effects of Aβ on cultured endothelial cells

Cell Types	Aβ Type	Pre-Aggregated Aβ Used	Concentration Range Tested	Incubation Time	Minimum Concentration Required	Molecular Mechanisms of Aβ	References
HBMEC	Aβ1–42	Yes	0.0125–1.25 μM	1 h	0.125 μM	Upregulation of C-C chemokine receptor type 5 via JNK, ERK, PI3K activation through RAGE	109
HBMEC	Aβ1–42	Yes	0.001–10 μM	24 h	0.01 μM	Increased production of hydrogen peroxide through RAGE	25
HBEC	Aβ1–40	Yes	1–20 μM	2, 4, 8, 12 h	5 μM	Increase in inflammatory markers MCP-1, IL-8, IL-6, GRO via AP-1 transcription	184
MCEC	Aβ25–35	Yes	2.5–40 μM	24 h	20 μM	Decreased heat shock protein 90, p-Akt, telomerase reverse transcriptase, cyclin-dependent kinase 4	29
	Aβ1–40
MCEC	Aβ25–35	—	25 μM	24 h	25 μM	Activation of AP-1/pro-apoptotic protein Bim and Smac release	197
MCEC	Aβ25–35	—	0.01–50 μM	24 h	1 μM	Apoptosis via activation of caspase-8/caspase-3, mitochondrial dysfunction	194
MCEC	Aβ25–35	Yes	20 μM	24 h	20 μM	Activation of apoptosis signal-regulating kinase 1 leading Bax increase via phosphorylations of p53 and p38-MAPK	80
Rat brain EC	Aβ25–35	—	47–380 μM	72 h	188 μM	Cell toxicity via increased LDH release and decreased glucose consumption	149
Mouse brain EC line	Aβ1–40	—	0.3 μM	30 min	0.3 μM	PARP activation via oxidative-nitrosative stress, increase in intracellular Ca2+	144
BAEC	Aβ1–42	No	0.05–2.2 μM	1–5 min	0.22 μM	Increased Ca2+-influx	12
BAEC, RMCEC	Aβ1–40	—	0.1–1 μM	30 min	0.1 μM	Stimulation of cGMP production, release of kinins	190
BAEC	Aβ25–35	—	1 μM	24 h	1 μM	Impaired activation of K+-channels and reduced nitrite production	28
BAEC	Aβ25–35	—	0.1–1000 nM	24 h	1 nM	Reduced nitrite production	150
	Aβ1–40	—	0.1–1000 nM	24 h	10 nM
BAEC	Aβ25–35	Yes	1 μM	24 h	1 μM	Production of reactive oxygen species, blockade of agonist-stimulated eNOS phosphorylation at Ser1179, decreased nitric oxide production	104
	Aβ1–42		5 μM	24 h	5 μM
HAEC	Aβ25–35	—	Up to 40 μM	30 min to 24 h	5 μM	Apoptosis, necrosis via reactive oxygen species, increase in intracellular Ca2+	169
	Aβ1–42		Up to 32 μM		4 μM
Porcine PAEC	Aβ25–35	Yes	1–50 μM	18 h	20 μM	Apoptosis, increased free radicals production, dysregulation of Ca2+ homeostasis, impaired glucose uptake	14
				24 h	5 μM

EC, endothelial cells; HBMEC, human brain microvessel endothelial cells; HBEC, human brain endothelial cells; MCEC, mouse cerebral endothelial cells; BAEC, bovine aortic endothelial cells; RMCEC, rat microvascular coronary endothelial cells; HAEC, human aortic endothelial cells; PAEC, pulmonary aortic endothelial cells; Aβ, amyloid-β; RAGE, receptor for advanced glycation end products; Akt, protein kinase B; MAPK, mitogen-activated protein kinase; AP-1, activator protein 1; JNK, c-Jun NH₂-terminal kinase; ERK, extracellular signal-regulated kinase; PI3K, phosphoinositide 3-kinases; MCP-1, monocyte chemoattractant protein-1; IL-6, interleukin-6; IL-8, interleukin-8; GRO, growth-regulated oncogene; LDH, lactate dehydrogenase; eNOS, endothelial nitric oxide synthase; cGMP, cyclic guanosine 3′,5′-monophosphate; -, unknown or not tested.