Recognition Functions of Pentameric C-Reactive Protein in Cardiovascular Disease

被引:31
作者
Agrawal, Alok [1 ]
Gang, Toh B. [1 ]
Rusinol, Antonio E. [1 ]
机构
[1] E Tennessee State Univ, Quillen Dishner Coll Med, Dept Biomed Sci, Johnson City, TN 37614 USA
关键词
LOW-DENSITY-LIPOPROTEIN; FOAM-CELL-FORMATION; ATHEROSCLEROTIC LESIONS; APOPTOTIC CELLS; IMMUNOHISTOCHEMICAL LOCALIZATION; INFARCT SIZE; OXIDIZED LDL; COMPLEMENT; BINDING; MACROPHAGES;
D O I
10.1155/2014/319215
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
C-reactive protein (CRP) performs two recognition functions that are relevant to cardiovascular disease. First, in its native pentameric conformation, CRP recognizes molecules and cells with exposed phosphocholine (PCh) groups, such as microbial pathogens and damaged cells. PCh-containing ligand-bound CRP activates the complement system to destroy the ligand. Thus, the PCh-binding function of CRP is defensive if it occurs on foreign pathogens because it results in the killing of the pathogen via complement activation. On the other hand, the PCh-binding function of CRP is detrimental if it occurs on injured host cells because it causes more damage to the tissue via complement activation; this is how CRP worsens acute myocardial infarction and ischemia/reperfusion injury. Second, in its nonnative pentameric conformation, CRP also recognizes atherogenic low-density lipoprotein (LDL). Recent data suggest that the LDL-binding function of CRP is beneficial because it prevents formation of macrophage foam cells, attenuates inflammatory effects of LDL, inhibits LDL oxidation, and reduces proatherogenic effects of macrophages, raising the possibility that nonnative CRP may show atheroprotective effects in experimental animals. In conclusion, temporarily inhibiting the PCh-binding function of CRP along with facilitating localized presence of nonnative pentameric CRP could be a promising approach to treat atherosclerosis and myocardial infarction. There is no need to stop the biosynthesis of CRP.
引用
收藏
页数:6
相关论文
共 91 条
[61]   C-reactive protein inhibits in vitro oxidation of low-density lipoprotein [J].
Rufail, Miguel L. ;
Ramage, Samuel C. ;
van Antwerpen, Rik .
FEBS LETTERS, 2006, 580 (22) :5155-5160
[62]  
SAXENA U, 1987, J BIOL CHEM, V262, P3011
[63]   Elevated C-reactive protein in atherosclerosis - Chicken or egg? [J].
Schunkert, Heribert ;
Samani, Nilesh J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (18) :1953-1955
[64]   Three dimensional structure of human C-reactive protein [J].
Shrive, AK ;
Cheetham, GMT ;
Holden, D ;
Myles, DAA ;
Turnell, WG ;
Volanakis, JE ;
Pepys, MB ;
Bloomer, AC ;
Greenhough, TJ .
NATURE STRUCTURAL BIOLOGY, 1996, 3 (04) :346-354
[65]   C-reactive protein-bound enzymatically modified low-density lipoprotein does not transform macrophages into foam cells [J].
Singh, Sanjay K. ;
Suresh, Madathilparambil V. ;
Prayther, Deborah C. ;
Moorman, Jonathan P. ;
Rusinol, Antonio E. ;
Agrawal, Alok .
JOURNAL OF IMMUNOLOGY, 2008, 180 (06) :4316-4322
[66]   The connection between C-reactive protein and atherosclerosis [J].
Singh, Sanjay K. ;
Suresh, Madathilparambil V. ;
Voleti, Bhavya ;
Agrawal, Alok .
ANNALS OF MEDICINE, 2008, 40 (02) :110-120
[67]   Exposing a Hidden Functional Site of C-reactive Protein by Site-directed Mutagenesis [J].
Singh, Sanjay K. ;
Thirumalai, Avinash ;
Hammond, David J., Jr. ;
Pangburn, Michael K. ;
Mishra, Vinod K. ;
Johnson, David A. ;
Rusinol, Antonio E. ;
Agrawal, Alok .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (05) :3550-3558
[68]   The binding of C-reactive protein, in the presence of phosphoethanolamine, to low-density lipoproteins is due to phosphoethanolamine-generated acidic pH [J].
Singh, Sanjay K. ;
Hammond, David J., Jr. ;
Beeler, Bradley W. ;
Agrawal, Alok .
CLINICA CHIMICA ACTA, 2009, 409 (1-2) :143-144
[69]   Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats [J].
Singh, U. ;
Dasu, M. R. ;
Yancey, P. G. ;
Afify, A. ;
Devaraj, S. ;
Jialal, I. .
JOURNAL OF LIPID RESEARCH, 2008, 49 (05) :1015-1023
[70]   Oxidation of low-density lipoproteins induces amyloid-like structures that are recognized by macrophages [J].
Stewart, CR ;
Tseng, AA ;
Mok, YF ;
Staples, MK ;
Schiesser, CH ;
Lawrence, LJ ;
Varghese, JN ;
Moore, KJ ;
Howlett, GJ .
BIOCHEMISTRY, 2005, 44 (25) :9108-9116