Serum amyloid P component: A novel potential player in vessel degeneration in CADASIL

• Published in: Journal of the neurological sciences Vol. 379; pp. 69 - 76
• Main Authors: Nagatoshi, Akihito, Ueda, Mitsuharu, Ueda, Akihiko, Tasaki, Masayoshi, Inoue, Yasuteru, Ma, Yihong, Masuda, Teruaki, Mizukami, Mayumi, Matsumoto, Sayaka, Kosaka, Takayuki, Kawano, Takayuki, Ito, Takaaki, Ando, Yukio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2017
• Subjects: Aged; Aged, 80 and over; CADASIL; CADASIL - genetics; CADASIL - metabolism; CADASIL - pathology; Female; Granular osmiophilic material; Humans; Male; Middle Aged; Neurology; NOTCH3; Periostin; Proteomic; Receptor, Notch3 - analysis; Receptor, Notch3 - biosynthesis; Receptor, Notch3 - genetics; Serum amyloid P component; Serum Amyloid P-Component - analysis; Serum Amyloid P-Component - biosynthesis; Serum Amyloid P-Component - genetics; Temporal Arteries - metabolism; Temporal Arteries - pathology; NOTCH3; CAA; LMD; SAP; GOM; Proteomic; Granular osmiophilic material; TBST; EDTA; BSA; LC-MS/MS; SDS-PAGE; CADASIL; FAP; PBST; RT-PCR; Periostin; TGF-β; Serum amyloid P component; CPHPC; ELISA; granular osmiophilic material; serum amyloid P component; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; ( R)-1-[6-[( R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid; reverse transcription-polymerase chain reaction; cerebral amyloid angiopathy; familial amyloid polyneuropathy; liquid chromatography–tandem mass spectrometry; ethylenediaminetetraacetic acid; phosphate-buffered saline with Tween 20; Tris-buffered saline plus Tween 20; cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; transforming growth factor-β; enzyme-linked immunosorbent assay; laser microdissection; bovine serum albumin
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2017.05.033

In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), granular osmiophilic material (GOM) may play some roles in inducing cerebrovascular events. To elucidate the pathogenesis of CADASIL, we used laser microdissection and liquid chromatography–tandem mass spectrometry to analyze cerebrovascular lesions of patients with CADASIL for GOM. The analyses detected serum amyloid P component (SAP), annexin A2, and periostin as the proteins with the largest increase in the samples, which also demonstrated NOTCH3. For the three proteins, anti-human SAP antibody had the strongest reaction in the lesions where the anti-human NOTCH3 antibody showed positive staining. Moreover, immunofluorescence staining with the two antibodies clearly showed co-localization of SAP and NOTCH3. mRNA analyses indicated no positive SAP expression in the brain materials, which suggested that the source of SAP found in the GOM was only the liver. A solid phase enzyme-linked immunosorbent assay confirmed the binding of SAP with NOTCH3. Serum SAP concentrations were neither up-regulated nor down-regulated in CADASIL patients, when compared with those in control subjects. SAP may play an important role in GOM formation although precise mechanisms remain to be elucidated. •SAP, annexin A2, and periostin were found in vessels of CADASIL.•SAP and NOTCH3 were clearly co-localized in vessels of CADASIL.•SAP derived from liver bound to NOTCH3 and they were simultaneously involved in GOM.