Acute-Phase Proteins Before Cerebral Ischemia in Stroke-Prone Rats: Identification by Proteomics

Background and Purpose— 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, &agr;2-HS-glycoprotein, kallikrein-binding protein, &agr;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.

[1]  R. Aebersold,et al.  Proteins of rat serum V: Adjuvant arthritis and its modulation by nonsteroidal anti‐inflammatory drugs , 2000, Electrophoresis.

[2]  T. Ikizler.  What Are the Causes and Consequences of the Chronic Inflammatory State in Chronic Dialysis Patients? , 2000, Seminars in dialysis.

[3]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[4]  R. Aebersold,et al.  A web site for the Rat Serum Protein Study Group , 1999, Electrophoresis.

[5]  K. Lindpaintner,et al.  Altered structure, regulation, and function of the gene encoding the atrial natriuretic peptide in the stroke-prone spontaneously hypertensive rat. , 1999, Circulation research.

[6]  W. Reinhart,et al.  C-reactive protein (CRP) in cerebro-vascular events. , 1999, Atherosclerosis.

[7]  P. Ridker,et al.  The gene encoding atrial natriuretic peptide and the risk of human stroke. , 1999, Circulation.

[8]  F. Barone,et al.  Inflammatory Mediators and Stroke: New Opportunities for Novel Therapeutics , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  K. Lees,et al.  C-reactive protein and outcome after ischemic stroke. , 1999, Stroke.

[10]  W. Blackstock,et al.  Proteomics: quantitative and physical mapping of cellular proteins. , 1999, Trends in biotechnology.

[11]  Á. Chamorro,et al.  Cytokine-induced inflammation and long-term stroke functional outcome , 1999, Journal of the Neurological Sciences.

[12]  G. Jansen,et al.  Cerebral Edema , and Proteinuria in Stroke-Prone Hypertensive Rats Receptor Blockade Can Modulate − Early-Onset , 1999 .

[13]  I. Miller,et al.  Proteins of rat serum IV. Time‐course of acute‐phase protein expression and its modulation by indomethacine , 1999, Electrophoresis.

[14]  R. Aebersold,et al.  Proteins of rat serum: III. Gender‐related differences in protein concentration under baseline conditions and upon experimental inflammation as evaluated by two‐dimensional electrophoresis , 1999, Electrophoresis.

[15]  C. Stier,et al.  Downloaded from http://hyper.ahajournals.org / by guest on February 21, 2013Role of Aldosterone in Renal Vascular Injury in Stroke-Prone Hypertensive Rats , 2022 .

[16]  G. Jansen,et al.  Early-onset but not late-onset endothelin-A-receptor blockade can modulate hypertension, cerebral edema, and proteinuria in stroke-prone hypertensive rats. , 1999, Hypertension.

[17]  Denis F. Hochstrasser,et al.  Proteome in Perspective , 1998, Clinical chemistry and laboratory medicine.

[18]  G. Jansen,et al.  Enalapril prevents imminent and reduces manifest cerebral edema in stroke-prone hypertensive rats. , 1998, Stroke.

[19]  R. Aebersold,et al.  Proteins of rat serum: II. Influence of some biological parameters of the two‐dimensional electrophoresis pattern , 1998, Electrophoresis.

[20]  R. Aebersold,et al.  Proteins of rat serum: I. Establishing a reference two‐dimensional electrophoresis map by immunodetection and microbore high performance liquid chromatography‐electrospray mass spectrometry , 1998, Electrophoresis.

[21]  P. Ridker,et al.  Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. , 1998, Circulation.

[22]  D. Ganten,et al.  Impaired vasorelaxant responses to natriuretic peptides in the stroke‐prone phenotype of spontaneously hypertensive rats , 1998, Journal of hypertension.

[23]  M. Koyama,et al.  Preventive and therapeutic effects of AE0047 on renal injury in stroke-prone spontaneously hypertensive rats , 1998 .

[24]  K. Lindpaintner,et al.  Endothelial dysfunction and genetic predisposition to stroke in spontaneously hypertensive rats , 1998 .

[25]  G. Jansen,et al.  Proteinuria precedes cerebral edema in stroke-prone rats: a magnetic resonance imaging study. , 1998, Stroke.

[26]  C. Stier,et al.  Regional renal nitric oxide release in stroke-prone spontaneously hypertensive rats. , 1997, Hypertension.

[27]  M. Koyama,et al.  PREVENTATIVE AND THERAPEUTIC EFFECTS OF AE0047 ON RENAL INJURY IN STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS , 1997, Clinical and experimental pharmacology & physiology.

[28]  A. Pasternack,et al.  Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment. , 1996, European heart journal.

[29]  P. Bruneval,et al.  Losartan's Protective Effects in Stroke‐Prone Spontaneously Hypertensive Rats Persist Durably After Treatment Withdrawal , 1993, Journal of cardiovascular pharmacology.

[30]  O. Vesterberg,et al.  Electrophoresis and silver staining of rat urinary proteins including alpha 2u-globulin (rat n II). , 1992, Applied and theoretical electrophoresis : the official journal of the International Electrophoresis Society.

[31]  J. Garrels.  The QUEST system for quantitative analysis of two-dimensional gels. , 1989, The Journal of biological chemistry.

[32]  C. Stier,et al.  Enalapril Prevents Stroke and Kidney Dysfunction in Salt‐Loaded Stroke‐Prone Spontaneously Hypertensive Rats , 1989, Hypertension.

[33]  L. Feld,et al.  Age-Related Changes in Serum Proteins of the Spontaneously Hypertensive Rat , 1988, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[34]  H. Endo,et al.  Length polymorphism in the 3′ noncoding region of rat hepatic α2u-globulin mRNAs , 1987 .

[35]  G. Howlett,et al.  Major acute phase α1‐protein of the rat is homologous to bovine kininogen and contains the sequence for bradykinin: its synthesis is regulated at the mRNA level , 1985, FEBS letters.

[36]  P. Righetti,et al.  Non‐linear pH courses with immobilized pH gradients , 1985 .

[37]  Y. Yamori,et al.  Possible role of nutritional factors in the incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats. , 1984, Hypertension.

[38]  M. Pepys,et al.  Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. , 1983, Advances in immunology.

[39]  G. Howlett,et al.  The acute phase response of plasma protein synthesis during experimental inflammation. , 1982, The Journal of biological chemistry.

[40]  P. Arnaud,et al.  Marker proteins in inflammation , 1982 .

[41]  F. Deerberg,et al.  Proteinuria in rats in relation to age-dependent renal changes , 1980, Laboratory animals.

[42]  G. Schreiber,et al.  A rat serum glycoprotein whose synthesis rate increases greatly during inflammation. , 1979, The Journal of biological chemistry.

[43]  A. Nagaoka,et al.  Renin-angiotensin system in stroke-prone spontaneously hypertensive rats. , 1979, The American journal of physiology.

[44]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[45]  A. Nagaoka,et al.  Genetic predisposition to stroke in spontaneously hypertensive rats. , 1976, The American journal of physiology.

[46]  O. Neuhaus,et al.  The effect of dietary protein on the excretion of α2u, the sex-dependent protein of the adult male rat , 1975 .

[47]  G. Buckberg,et al.  Regional Myocardial Blood Flow in Lambs with Concentric Right Ventricular Hypertrophy , 1974, Circulation research.

[48]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.