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α-Synuclein was originally identified as the precursor of non-amyloid β component of Alzheimer''s disease amyloid (NAC). NAC is detected in cerebral amyloid angiopathy; and we studied whether cerebral vascular cells express α-synuclein. Immunohistochemical studies of normal human cerebral tissues revealed the expression of α-synuclein in vascular endothelial and smooth muscle cells. Also cultures of human umbilical vein endothelial cells and umbilical artery smooth muscle cells were found, by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis, to constitutively express α-synuclein mRNA. Western blot analysis disclosed the presence of α-synuclein protein in lysates of these cells. We conclude that vascular cells express α-synuclein, and it may play some role in the physiology of the vascular wall. [Copyright &y& Elsevier]

The non-amyloid β component of Alzheimer''s disease amyloid (NAC) is detected in cerebral amyloid angiopathy; and the precursor of NAC is now known to be identical to α-synuclein (α-S), a major component of Lewy bodies in Parkinson''s disease. We studied if cerebral vascular cells express α-S. Immunohistochemical studies of human cerebral tissues from control and cerebral amyloid angiopathy patients revealed the expression of α-S in vascular endothelial and smooth muscle cells. Then we studied the expression of α-S in vitro using cultures of vascular cells. Cultures of human umbilical vein endothelial cells and umbilical artery smooth muscle cells were found to constitutively express α-S messenger RNA and protein. α-S is normally expressed in vascular cells and may play some physiological role in the vascular wall. [Copyright &y& Elsevier]

Abstract: Mutations in the parkin gene are related with early-onset Parkinson''s disease. Parkin is identified as an E3-ligase that combines target proteins with ubiquitin. α-Synuclein and synphilin-1 are substrates for E3-ligase activity of parkin and considered to be involved in the pathogenesis of Parkinson''s disease. We previously demonstrated both α-synuclein and synphilin-1 are expressed in vascular endothelial cells (VEC). In the present study, we addressed possible expression of parkin in VEC. Parkin immunoreactivity was detected in vascular endothelial cells in postmortem human brain. Expressions of parkin mRNA and protein in human umbilical vein endothelial cells (HUVEC) were demonstrated by reverse-transcription polymerase-chain reaction (RT-PCR) and western blotting. Expression of parkin in HUVEC was not altered with tunicamycin treatment, which exerts unfolded protein stress on cells. We conclude that parkin is expressed in VEC, and that unfolded protein stress may not regulate its expression. [Copyright &y& Elsevier]

Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of major hematopoietic growth factors, activates mature leukocytes. GM-CSF is produced by endothelial cells stimulated with lipopolysaccharide (LPS), and the LPS-induced GM-CSF production may play an important role in the activation of neutrophils on the endothelial surface. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a ligand for peroxisome proliferator-activated receptor-γ (PPAR-γ) and modulates inflammatory reactions by regulating the expression of various genes. We studied the effect of 15d-PGJ2 on the LPS-induced GM-CSF expression in endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured and the expressions of GM-CSF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. 15d-PGJ2 inhibited the LPS-induced GM-CSF expression in a concentration-dependent manner; but ciglitazone, another agonist for PPAR-γ, had no effect. This suggests that 15d-PGJ2 inhibits GM-CSF expression through a mechanism unrelated to PPAR-γ. 15d-PGJ2 induced, by itself, the expression of interleukin-8, a potent proinflammatory chemokine, in HUVEC. 15d-PGJ2 may regulate inflammatory reactions by controlling the balance of various cytokines. [Copyright &y& Elsevier]