C-reactive protein (CRP) is a pentraxin that is mainly synthesized in the liver in response to inflammatory cytokines. It exists in two functionally and structurally distinct isoforms. The first is a highly pro-inflammatory and mostly tissue-bound monomeric isoform (mCRP). The second is circulating pentameric CRP (pCRP), which also serves as a substrate for the formation of mCRP. CRP is elevated during inflammatory conditions and is associated with a higher risk of cardiovascular disease. The aim of this review is to examine the current state of knowledge regarding the role of these two distinct CRP isoforms on atherogenesis. This should allow further evaluation of CRP as a potential therapeutic target for atherosclerosis. While it seems clear that CRP should be used as a therapeutic target for atherosclerosis and cardiovascular disease, questions remain about how this can be achieved. Current data suggests that CRP is more than just a biomarker of atherosclerosis and cardiovascular disease. Indeed, recent evidence shows that mCRP in particular is strongly atherogenic, whereas pCRP may be partially protective against atherogenesis. Thus, further investigation is needed to determine how the two CRP isoforms contribute to atherogenesis and the development of cardiovascular disease.

Flavonoid aglycones are secondary plant metabolites that exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and antiplatelet effects. However, the precise molecular mechanisms underlying their inhibitory effect on platelet activation remain poorly understood. In this study, we applied flow cytometry to analyze the effects of six flavonoid aglycones (luteolin, myricetin, quercetin, eriodictyol, kaempferol, and apigenin) on platelet activation, phosphatidylserine externalization, formation of reactive oxygen species, and intracellular esterase activity. We found that these compounds significantly inhibit thrombin-induced platelet activation and decrease formation of reactive oxygen species in activated platelets. The tested aglycones did not affect platelet viability, apoptosis induction, or procoagulant platelet formation. Notably, luteolin, myricetin, quercetin, and apigenin increased thrombin-induced thromboxane synthase activity, which was analyzed by a spectrofluorimetric method. Our results obtained from Western blot analysis and liquid chromatography–tandem mass spectrometry demonstrated that the antiplatelet properties of the studied phytochemicals are mediated by activation of cyclic nucleotide-dependent signaling pathways. Specifically, we established by using Förster resonance energy transfer that the molecular mechanisms are, at least partly, associated with the inhibition of phosphodiesterases 2 and/or 5. These findings underscore the therapeutic potential of flavonoid aglycones for clinical application as antiplatelet agents.