P-selectin (CD62) is a rapidly inducible cell surface adhesion molecule that is expressed on platelets and endothelial cells and mediates their interaction with leukocytes. In vitro studies have suggested that this receptor may play an important role in hemostasis and in inflammatory response to tissue injury. We report the molecular cloning and sequencing of murine cDNA for P-selectin. The lectin, epidermal growth factor (EGF)-like, transmembrane, and cytoplasmic domains are highly conserved between mouse and human, with an overall amino acid identity of 79%. To further investigate the biology of this adhesion molecule in vivo, we analyzed mRNA levels for P-selectin in mice after injection with endotoxin. Northern blot data indicate that the cellular response in vivo includes a rapid increase in the level of mRNA, presumably for new synthesis of P-selectin. The increase in mRNA is maximal at 4 hours, and turnover is relatively rapid, with levels of RNA having decreased substantially by 6 hours following stimulation with endotoxin. After administration of endotoxin, the highest levels of mRNA expression were detected in liver, lung, kidney, and heart.
Background/Introduction Cigarette smoking is associated with increased risk of cardiovascular (CV) events with effective treatment currently limited to smoking cessation. REDUCE-IT, a multinational, double-blind trial, randomised 8179 statin-treated patients with controlled low density lipoprotein cholesterol, elevated triglycerides, and CV risk, to icosapent ethyl (IPE) 4 grams/day or placebo, with a median of 4.9 years of follow-up. IPE reduced the primary composite (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularisation, or hospitalisation for unstable angina) and key secondary composite (CV death, nonfatal MI, or nonfatal stroke) endpoints 25% and 26%, respectively (each P<0.0001), and individual components including stroke (28%), MI (31%), cardiac arrest (48%), and sudden cardiac death (31%) (all P≤0.01). Purpose To evaluate the effects of IPE on the risk of CV events and safety measures in patients by history of smoking. Methods The effect of IPE on first and total primary and key secondary endpoints was evaluated in the REDUCE-IT study using post hoc analyses based upon smoking history. Groups were classified as never smokers (n=3264), former smokers (n=3672), and current smokers (n=1241). Results Compared with placebo, IPE use in combined current and former smokers (n=4913) was associated with significant reductions in time to the primary composite endpoint (hazard ratio, 0.77 [95% CI, 0.68–0.87]; P<0.0001) and in total events (rate ratio, 0.71 [95% CI, 0.61–0.82]; P<0.0001) (Figure 1). These benefits remained significant when subdivided into current and former smokers and were associated with reductions in the key secondary composite endpoint (P=0.04, P=0.005), and the individual components of CV death or nonfatal MI (P=0.04, P=0.01) and fatal or nonfatal MI (P=0.009, P=0.01, respectively). Never smokers also had a significant benefit from IPE for both the primary and key secondary endpoints. Overall, there were similar estimated rates of first occurrences of CV death, MI, stroke, coronary revascularisation, or hospitalisation for unstable angina in current smokers (23.8%) and former smokers (23.0%) assigned to IPE compared with never smokers on placebo (25.7%) (Figure 2). Conclusions In the REDUCE-IT study, IPE treatment significantly reduced the risk of CV events in current and former smokers to levels observed in never smokers. While smoking cessation should always be recommended, these data raise the possibility that IPE treatment may markedly attenuate the CV hazards attributable to smoking. Funding Acknowledgement Type of funding sources: None.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.