scholarly journals Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Alexander J. Szalai ◽  
Mark A. McCrory ◽  
Dongqi Xing ◽  
Fadi G. Hage ◽  
Andrew Miller ◽  
...  

Raised blood C-reactive protein (CRP) level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO) drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery). Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation). CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Kenji Inoue ◽  
Tatsuhiko Kodama ◽  
Hiroyuki Daida

Numerous studies have recently examined the role of pentraxin 3 (PTX3) in clinical situations. The pentraxin family includes C-reactive protein (CRP); however, unlike CRP, PTX3 is expressed predominantly in atherosclerotic lesions that involve macrophages, neutrophils, dendritic cells, or smooth muscle cells. Interestingly, PTX3 gene expression in human endothelial cells is suppressed to a greater extent by pitavastatin than the expression of 6,000 other human genes that have been examined, suggesting that PTX3 may be a novel biomarker for inflammatory cardiovascular disease. The expression and involvement of PTX3 in cardiovascular diseases are discussed in this paper, along with the characteristics of PTX3 that make it a suitable biomarker; namely, that the physiological concentration is known and it is independent of other risk factors. The results discussed in this paper suggest that further investigations into the potential novel use of PTX3 as a biomarker for inflammatory cardiovascular disease should be undertaken.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Oliver Zimmermann ◽  
Kefei Li ◽  
Myron Zaczkiewicz ◽  
Matthias Graf ◽  
Zhongmin Liu ◽  
...  

The role of C-reactive protein (CRP) in atherosclerosis is controversially discussed. Whereas initial experimental studies suggested a pathogenic role for CRP in atherogenesis, more recent genetic data from Mendelian randomization trials failed to provide evidence for a causative role of CRP in cardiovascular disease. Also, experimental results from laboratories all over the world were indeed contradictory, partly because of species differences in CRP biology and partly because data were not accurately evaluated. Here we summarize the published data from experimental work with mainly human material in order to avoid confusion based on species differences in CRP biology. Experimental work needs to be reevaluated after reconsideration of some traditional rules in research: (1) in order to understand a molecule’s role in disease it may be helpful to be aware of its role in physiology; (2) it is necessary to define the disease entity that experimental CRP research deals with; (3) the scientific consensus is as follows: do not try to prove your hypothesis. Specific CRP inhibition followed by use of CRP inhibitors in controlled clinical trials may be the only way to prove or disprove a causative role for CRP in cardiovascular disease.


2016 ◽  
Vol 94 (7) ◽  
pp. 497-503 ◽  
Author(s):  
A. F. Verbovoy ◽  
Lyudmila A. Sharonova ◽  
O. V. Kosareva ◽  
N. I. Verbovaya ◽  
Yu. A. Dolgikh

The article presents data on the relationship between thyroid dysfunction and cardiovascular diseases. The role of dyslipidemia, adipokines (adiponectin, leptin, resistin), C-reactive protein, deficiency of vitamin D3 in the development of cardiovascular disease in hypothyroidism is discussed. The article describes characteristics of myocardial remodeling, its dysfunction and their correlation with risk factors of cardiovascular diseases in patients with hypothyroidism.


Critical Care ◽  
2011 ◽  
Vol 15 (S3) ◽  
Author(s):  
S Das ◽  
D Anand ◽  
S Ray ◽  
S Bhargava ◽  
A Manocha ◽  
...  

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e002038
Author(s):  
Carina Borst ◽  
Farideh Alasti ◽  
Josef S Smolen ◽  
Daniel Aletaha

ObjectiveTo determine the contribution of clinical and biochemical inflammation to structural progression of patients with psoriatic arthritis (PsA).MethodsWe analysed patients from the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 trial (infliximab vs placebo). We obtained total modified Sharp/van-der-Heijde Scores from baseline and year one images, and swollen joint counts (SJC) and levels of C reactive protein (CRP) throughout the second half of year 1 (5 measurements) from 74 placebo-treated patients. We computed radiographic progression, time-averaged SJC (taSJC) and CRP (taCRP) values and assessed their impact on structural progression by logistic regression analysis. We further categorised patients as ‘active’ (+) or ‘inactive’ (−) based on their taSJC (cut-off point: 2/66 joints) and taCRP (cut-off point: 0.5 mg/dL) and compared radiographic progression across three groups (double inactive, single active, double active).ResultsORs for progression were 1.24 (95 % CI 1.04 to 1.47; p=0.016) for taSJC and 6.08 (95 % CI 1.12 to 33.03; p=0.036) for taCRP. When predictors were dichotomised (+ vs −), differences were maintained between taSJC+ and taSJC− patients (1.05±3.21 and 0.56±2.30, respectively), as well as for taCRP+ vs taCRP− patients (1.14±3.23 and 0.05±2.37, respectively). Progression was intermediate in the presence of abnormalities of one but not the other inflammatory variable, indicating increasing radiographic progression with increasing inflammation (p=0.05).ConclusionIn patients with PsA, both clinical and biochemical inflammation have an impact on structural progression. Overall, progression is smallest in the absence of both clinical and biochemical inflammation, higher when either clinical or biochemical inflammation is present and highest with both clinical and biochemical inflammation.


2016 ◽  
Vol 9 (3) ◽  
pp. 63 ◽  
Author(s):  
Hassan Naji

<p><strong>OBJECTIVE: </strong>The main objective of the study was to investigate the role of C-reactive protein on the relationship between Bisphenol A &amp; Cardiovascular Disease, where the C-reactive protein has been taken as a moderating variable.</p><p><strong>METHODS: </strong>Quantitative research design has been incorporated for evaluating the role of C-reactive protein. Similarly, non-parametric Spearman correlation test has been conducted to assess the relationship between BPA and CVD. The data was taken out from the National Health and Nutrition Examination Survey (NHANES), which was collected in the year 2009-2010.</p><p><strong>RESULTS: </strong>The impact of urinary Bisphenol A on serum C-reactive protein was found statistically significant according to the Spearman correlation coefficient, <em>r</em>s<em>= </em>.06, <em>p </em>= .015. The scatter plots found that there is no relationship between the two variables; this observation held true after filtering the outliers from the plot.</p><p><strong>CONCLUSION:</strong> The results might have positive change by contributing to the body of knowledge on bisphenol A and by rising scientific examination of substances used by the people in the daily life. Further research to identify other possible causes of CVD and elevation of CRP is recommended.</p>


1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 144-149 ◽  
Author(s):  
Soon Bae Kim ◽  
Won Seok Yang ◽  
Jung Sik Park

Our objective was to review the articles about the association between hypoalbuminemia and atherosclerotic or thrombotic cardiovascular disease (CVD) and to look for possible explanations for the role of hypoalbuminemia. Increased incidences of CVD were reported in patients with hypoalbuminemia owing to renal or other diseases. Hypoalbuminemia increases plasma levels of lipoprotein(a), fibrinogen, and arachidonic acid metabolites; it also increases platelet aggregability and blood viscosity, all of which may contribute to the development of CVD. This cause-effect association is thought to be “dependent.” Changes in atherogenic lipoproteins or lipids, such as LDL cholesterol, triglycerides, and apolipoprotein B, are controversial in hypoalbuminemic dialysis patients, possibly because coexistent malnutrition and volume status can affect both albumin and lipids. In our recent study, there was a negative correlation between serum albumin and C-reactive protein, D-dimer (an index of intravascular thrombogenesis), and von Willebrand factor (a marker for endothelial cell injury), but infusion of albumin did not affect the level of these parameters, which suggests that the correlations may be an effect-effect association by a confounding variable, such as inflammation. In conclusion, hypoalbuminemia is associated with cardiovascular disease via two pathways: one, a “dependent” cause-effect association; the other, an effect-effect association.


Author(s):  
Amika Aggarwal ◽  
Sangeeta Pahwa

Background: Preterm birth is one of the most important cause of perinatal morbidity and mortality. PROM is defined as spontaneous rupture of membranes before the onset of uterine contraction. Objective of present study was to evaluate the role of CRP as an early predictor of Chorioamnionitis in PPROM.Methods: A prospective study was done on 50 cases with PPROM and 50cases of control group without PPROM. All mothers and babies were observed from the time of admission to the time of discharge.Results: C-reactive protein appears to be the most sensitive acute phase protein; rising of less than 24 hours makes it suitable to serve as a marker for diagnosing an infective process in early stage. On comparing C-reactive protein levels with other laboratory tests and indicators of infection (e.g. total leucocyte count DLC, maternal fever, maternal tachycardia, fetal tachycardia) we found CRP level to be more sensitive (100%) but less specific (69.56%) in identifying clinical Chorioamnionitis. The positive predictive value was 22.22% and negative predictive value was 100%.Conclusions: In cases of PPROM, raised CRP is an early predictor of clinical Chorioamnionitis as well as histological Chorioamnionitis.


Sign in / Sign up

Export Citation Format

Share Document