scholarly journals Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism

2018 ◽  
Vol 449 (1-2) ◽  
pp. 167-183 ◽  
Author(s):  
Rai Ajit K. Srivastava ◽  
Joseph A. Cornicelli ◽  
Bruce Markham ◽  
Charles L. Bisgaier
2012 ◽  
Vol 153 (22) ◽  
pp. 857-860 ◽  
Author(s):  
László Szapáry ◽  
Gergely Fehér

Statin therapy is the cornerstone of anti-atherosclerotic treatment, and it considered obligatory in the secondary prevention of atherosclerotic diseases. Rosuvastatin is well-known and efficacious lipid-lowering agent. Generic drugs are more frequently used instead of its ancestors. Generic rosuvastatin forms have been aproved recently to the Central European market, but their safety and efficacy have not been previously examined in cerebrovascular patient populations. Patients and methods: 109 patients with documented ischaemic cerebrovascular events were included in our study. 20 mg generic rosuvastatin significantly decreased total cholesterol (5.47 vs. 3.88 mmol/l, p<0.01), low-density lipoprotein (3.16 vs. 1.84 mmol/l, p<0.01) and trigliceride levels (1.77 vs. 1.33 mmol/l, p<0.05, and there was a non-significant high-density lipoprotein increasing tendency (1.27 vs. 1.36 mmol/l, p = 0.08). There was also a significant decrease in high-sensitive C-reactive protein levels (3.73 vs. 2.82 mg/l, p<0.05). Overall, 30% decrease in total cholesterol, 42% decrease in low-density lipoprotein, 25% decrease in trigliceride and high-sensitive C-reactive protein and 9% increase in high-density lipoprotein levels were observed. Conclusions: The generic rosuvastatin studied by the authors proved to be safe and efficacious lipid-lowering agent. Based on these short term results, in daily practice, generic rosuvastatin treatment seems to be cost-effective for the treatment of patients with ischemis cerebrovascular disease. Orv. Hetil., 2012, 153, 857–860.


2008 ◽  
Vol 54 (2) ◽  
pp. 343-349 ◽  
Author(s):  
Claudia Marsik ◽  
Lili Kazemi-Shirazi ◽  
Thomas Schickbauer ◽  
Stefan Winkler ◽  
Christian Joukhadar ◽  
...  

Abstract Background: C-reactive protein (CRP), an acute-phase protein, is a sensitive systemic marker of inflammation and acute-phase reactions. Testing CRP concentrations at hospital admission may provide information about disease risk and overall survival. Methods: All first-ever transmittals to the department of medical and chemical laboratory diagnostics for determination of low-sensitivity CRP (n = 274 515, 44.5% male, median age 51 years) between January 1991 and July 2003 were included [median follow-up time: 4.4 years (interquartile range, 2.3–7.4 years)]. The primary endpoint was all-cause mortality. Multivariate Cox regression adjusted for sex and age was applied for analysis. Results: Compared to individuals within the reference category (CRP &lt;5 mg/L), hazard ratios (HR) for all-cause mortality increased from 1.4 (5–10 mg/L category) to 3.3 in the highest category (&gt;80 mg/L, all P &lt;0.001). CRP was associated with various causes of death. The relation of CRP to cancer death was stronger than to vascular death. Younger patients with increased CRP had relatively far worse outcome than older patients (maximal HR: ≤30 years: 6.7 vs &gt;60 years: 1.7–3.7). Interestingly, both short- and long-term mortality were associated with increasing CRP concentrations (&gt;80 mg/L: HR 22.8 vs 1.4). Conclusion: Measurement of low-sensitivity CRP at hospital admission allowed for the identification of patients at increased risk of unfavorable outcome. Our findings indicate that close attention should be paid to hospitalized patients with high CRP not only because of very substantial short-term risk, but also long-term excess risk, the basis for which needs to be determined.


1982 ◽  
Vol 156 (1) ◽  
pp. 230-242 ◽  
Author(s):  
F C de Beer ◽  
A K Soutar ◽  
M L Baltz ◽  
I M Trayner ◽  
A Feinstein ◽  
...  

C-reactive protein (CRP), the classical acute-phase protein, can bind phospholipids by virtue of its specific, calcium-dependent reactivity with phosphorylcholine residues. However, analysis of acute-phase serum by gel filtration and by density gradient ultracentrifugation showed that the CRP was in a free, uncomplexed form, despite the coexistent presence of the various classes of serum lipoproteins, all of which contain phospholipids. In contrast, when isolated CRP was aggregated by immobilization at a sufficient density on a solid phase and then exposed to normal human serum, it selectively bound low density lipoprotein (LDL) and traces of very low density lipoprotein. The reaction was calcium dependent and reversible by free phosphorylcholine but not by heparin. LDL isolated from normal plasma was also bound by aggregated CRP. CRP reacts in vitro with a wide variety of different ligands both of extrinsic and of autogenous origin, e.g., microbial products and damaged cell membranes, respectively. If CRP aggregated in vivo by complexing with these ligands than acquires the capacity to selectively bind LDL, the phenomenon may have significant implications for the function of CRP and for the metabolism, clearance, and deposition of LDL.


1988 ◽  
Vol 253 (3) ◽  
pp. 851-857 ◽  
Author(s):  
A Mackiewicz ◽  
M K Ganapathi ◽  
D Schultz ◽  
D Samols ◽  
J Reese ◽  
...  

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.


1990 ◽  
Vol 68 (21) ◽  
pp. 1083-1083 ◽  
Author(s):  
H. Tilg ◽  
J. Mair ◽  
M. Herold ◽  
W. E. Aulitzky ◽  
P. Lechleitner ◽  
...  

Cardiology ◽  
2018 ◽  
Vol 141 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Yan Gao ◽  
Yan Qiu ◽  
Jihua Wu ◽  
Wei Diao ◽  
Haibo Zhang ◽  
...  

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular (CV) disease. Whether plasma PCSK9 measured during the acute phase predicts recurrent CV events in patients with acute myocardial infarction (AMI) remains unresolved. Methods and Results: Plasma PCSK9 levels were measured in 1,646 patients with AMI from the China PEACE-Prospective AMI Study at the acute phase. Additionally, 248 patients were resampled and measured at 1 month post-AMI. Associations of acute-phase PCSK9 tertiles with clinical characteristics and recurrent CV events within 1 year were assessed. Female gender (OR 1.94, 95% CI 1.24–3.03), premature coronary heart disease (CHD; OR 2.12, 95% CI 1.37–3.26), higher high-sensitivity C-reactive protein (OR 1.67, 95% CI 1.44–1.95), and higher triglycerides (OR 1.46, 95% CI 1.03–2.09) were associated with higher baseline PCSK9. Plasma PCSK9 levels in the highest tertile (versus lowest) did not have an increased risk of 1-year recurrent CV events in the AMI cohort (HR 0.78, 95% CI 0.52–1.16) or any subgroup. There was also no association between percentage changes in PCSK9 over the first month and 1-year recurrent events, although there was a trend of differences between patients in the upper versus lower tertiles. Conclusion: Plasma PCSK9 levels measured during the acute phase were associated with high-sensitivity C-reactive protein, triglycerides, premature CHD, and gender in patients with AMI but did not predict recurrent CV events within 1 year. Dynamic changes in PCSK9 suggested a trend yet no significance value in predicting recurrent CV events.


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