Acute-phase proteins before cerebral ischemia in stroke-prone rats: identification by proteomics.
OBJECTIVE
A high degree of proteinuria has been reported in stroke-prone spontaneously hypertensive rats (SHRSP). We studied the effect of salt loading on the detailed protein pattern of serum and urine in 3 rat strains: Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbred animal model for a complex form of cerebrovascular disorder resembling the human disease.


METHODS
Rats were given a permissive diet and received 1% NaCl in drinking water. The protein pattern in body fluids was assessed over time by 2-dimensional electrophoretic analysis. Brain alterations were monitored by MRI and histology.


RESULTS
Several proteins were excreted in urine after weeks of treatment and in advance of stroke: transferrin, hemopexin, albumin, alpha(2)-HS-glycoprotein, kallikrein-binding protein, alpha(1)-antitrypsin, Gc-globulin, and transthyretin. Markers of an inflammatory response, including very high levels of thiostatin, were detected in the serum of SHRSP at least 4 weeks before a stroke occurred.


CONCLUSIONS
In SHRSP subjected to salt loading, an atypical inflammatory condition and widespread alterations of vascular permeability developed before the appearance of anomalous features in the brain detected by MRI. Urinary concentrations of each of the excreted serum proteins correlated positively with time before stroke occurred.
Dipartimento di Scienze Farmacologiche, Facoltà di Farmacia, Università degli Studi, Milan, Italy.
L
L
Sironi
E
E
Tremoli
I
I
Miller
U
U
Guerrini
A M
AM
Calvio
I
I
Eberini
M
M
Gemeiner
M
M
Asdente
R
R
Paoletti
E
E
Gianazza
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D001798:Blood Proteins / Q000652:urine; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002545:Brain Ischemia / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D007249:Inflammation / Q000097:blood / Q000652:urine; D007704:Kininogens / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D011237:Predictive Value of Tests; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D012982:Sodium, Dietary / Q000494:pharmacology; D020521:Stroke / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D001798:Blood Proteins; D007704:Kininogens; D020543:Proteome; D012982:Sodium, Dietary