This review is focused on discussing the role of CRP in cardiovascular disease, including recent advances on the implication of CRP and its forms specifically on the pathogenesis of atherothrombosis and angiogenesis.
Many phenomena typically ascribed to inflammation or "chronic oxidative stress", such as the development of fatty streaks, "endothelial dysfunction," "vulnerable plaques," and the association of mild elevations of C-reactive protein and cytokines with atherothrombosis are better explained by hemorheologic and hemodynamic abnormalities, particularly elevated blood viscosity.
Although CRP is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased CV disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking.
While data regarding the pathogenetic role of C-reactive protein (CRP) in atherothrombosis are accumulating, it is still controversial whether local CRP secretion is of any pathobiological significance.
Although a direct role for CRP in atherothrombosis has been suggested, at the moment little is known about its involvement in the pathophysiology of acute coronary syndromes (ACS).
Human genetics demonstrate that genetic variation in the CRP gene is associated with lifelong increased CRP levels, but not with increased risk of atherothrombosis.
We therefore investigated spontaneous atherosclerosis and atherothrombosis, and systemic markers of inflammation (acute phase proteins), in aged, normal diet-fed, male apolipoprotein E deficient (apoE(-/-)) mice with and without transgenic expression of human CRP.
Polymorphisms of prostaglandin-endoperoxide synthase 2 gene, and prostaglandin-E receptor 2 gene, C-reactive protein concentrations and risk of atherothrombosis: a nested case-control approach.
In contrast to expected results, we found no association of Y402H polymorphism with risk of atherothrombosis (adjusted: myocardial infarction, OR=1.09, 95%CI 0.88-1.36, p=0.43; ischaemic stroke, OR=1.11, 95%CI 0.81-1.54, p=0.52; venous thromboembolism, OR=1.41, 95%CI 0.88-2.24, p=0.15), nor with baseline plasma C-reactive protein levels [median (interquartile range) mg/L: YY, 1.39 (0.70-2.60); YH, 1.10 (0.57-2.16); HH, 1.00 (0.48-1.79); p=0.14].
This study makes the novel observation that CRP induces PAI-1 expression and activity in HAECs and thus has implications for both the metabolic syndrome and atherothrombosis.
To assess PAI-1 antigen levels among subjects with type 2 diabetes mellitus (T2DM) plus Metabolic Syndrome (MetS) before clinical manifestations of atherothrombosis and the contribution of metabolic factors and 4G/5G polymorphism of PAI-1 gene on the variability of PAI-1.<i>Methods</i>.
Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of the fibrinolytic system and contributes to an increased risk of atherothrombosis in insulin-resistant obese patients.
This study makes the novel observation that CRP induces PAI-1 expression and activity in HAECs and thus has implications for both the metabolic syndrome and atherothrombosis.
The aims of this study were to observe associations of the genetic polymorphism for PAI-1 and t-PA with hypertension and atherothrombotic stroke, and to elucidate whether impaired fibrinolytic activity in atherothrombotic stroke was related to atherothrombosis per se or to other risk factors such as hypertension.
This association between PAI-1 and metabolic components of the Metabolic Syndrome could explain the predisposition of insulin resistant patients to atherothrombosis.
Plasma plasminogen activator inhibitor 1 (PAI-1) levels are elevated in insulin-resistant subjects and are associated with increased cardiovascular risk of atherothrombosis.