Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease.

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype.

Innate immune cell activation and epigenetic remodeling in symptomatic and asymptomatic atherosclerosis in humans in vivo.

Background And Aims: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis.

Differential effects of platelets and platelet inhibition by ticagrelor on TLR2- and TLR4-mediated inflammatory responses.

Platelets and platelet-monocyte interaction play an important role in inflammation. Both pro- and anti-inflammatory effects of platelet inhibition have been reported in animal models. This study aimed to investigate the effect of platelets and platelet inhibition by the new P2Y12 receptor antagonist ticagrelor on monocyte function, as assessed by cytokine responses to Toll-like Receptor (TLR) ligands.

Clinical impact of second-generation everolimus-eluting stent compared with first-generation drug-eluting stents in diabetes mellitus patients: insights from a nationwide coronary intervention register.

Objectives: This study sought to study the second-generation everolimus-eluting stent (EES) as compared with first-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in diabetes mellitus (DM) patients.

Background: There are limited data available comparing clinical outcomes in this setting with EES and SES, whereas studies comparing EES with PES are not powered for low-frequency endpoints.

Methods: All DM patients treated with EES, PES, or SES from January 18, 2007, to July 29, 2011, from the SCAAR (Swedish Coronary Angiography and Angioplasty Registery) were included.

Sympathoinhibition by atorvastatin in hypertensive patients.

Background: Experimental animal data suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) might reduce enhanced sympathetic activity, a hallmark of hypertensive patients. This hypothesis was tested for the first time in patients with primary hypertension.

Methods And Results: Using a prospective, randomized, placebo-controlled, double-blind, cross-over design, a proof-of-principle trial was performed in 13 patients with mild to moderate primary hypertension, who were randomly assigned to a regimen of atorvastatin (80mg/day) for 3 weeks, followed by placebo for 3 weeks or to a regimen of placebo for 3 weeks, followed by atorvastatin (80mg/day) for 3 weeks.

Alpha-receptor blockade improves muscle perfusion and glucose uptake in heart failure.

Aims: Alpha-adrenergic receptor-mediated vasoconstriction might underlie the insulin resistance seen in conditions associated with increased sympathetic tone, like chronic heart failure (CHF). Alpha-adrenergic receptor blockade by phentolamine could improve forearm blood flow (FBF) and forearm glucose uptake (FGU) in CHF patients.

Methods And Results: In 8 CHF patients and in 12 healthy volunteers, FBF (plethysmography) and FGU were measured in both forearms during a 150 min hyperinsulinaemic euglycaemic clamp procedure.

Improving myocardial perfusion by percutaneous coronary intervention reduces central sympathetic activity in stable angina.

Background: By stimulating sympathetic afferents, repetitive myocardial ischemia induces a state of increased sympathetic tone.

Hypothesis: Removing the ischemic trigger by revascularization using percutaneous coronary intervention (PCI) might thus reduce central sympathetic activity in symptomatically stable angina patients.

Methods: A total of 20 patients with stable angina > or = New York Heart Association (NYHA) class II with persistent symptoms despite maximal pharmacological therapy and a clinical indication for PCI, were included in our study.

Effect of PCI on inflammatory markers, adiponectin and insulin resistance.

Aims: Percutaneous coronary interventions (PCI) evoke an inflammatory response and have been reported to decrease adiponectin levels. If persistent over time, the inflammatory response and low adiponectin levels would induce insulin resistance, rendering PCI potentially hazardous for glucose metabolism. We investigated whether PCI decreased insulin sensitivity after one month and if so, whether this was related to a lasting elevation of inflammatory markers and decrease in adiponectin levels.

Sympathoinhibitory effect of statins in chronic heart failure.

Objectives: Increased (central) sympathetic activity is a key feature of heart failure and associated with worse prognosis. Animal studies suggest that statin therapy can reduce central sympathetic outflow. This study assessed statin effects on (central) sympathetic activity in human chronic heart failure (CHF) patients.