Stratification of acute myocardial and endothelial cell injury, salvage index and final infarct size by systematic microRNA profiling in acute ST-elevation myocardial infarction.

Aim: Acute injury and subsequent remodelling responses to ST-segment elevation myocardial infarction (STEMI) are major determinants of clinical outcome. Current imaging and plasma biomarkers provide delayed readouts of myocardial injury and recovery. Here, we sought to systematically characterize all microRNAs (miRs) released during the acute phase of STEMI and relate miR release to magnetic resonance imaging (MRI) findings to predict acute and late responses to STEMI, from a single early blood sample.

The relationship of perivascular adipose tissue and atherosclerosis in the aorta and carotid arteries, determined by magnetic resonance imaging.

Background And Aims: Imaging studies have relied on the 'overall' volumetric quantification of perivascular adipose tissue. We sought to assess the relationship of circumferential distribution between perivascular adipose tissue and adjacent wall thickness of carotid and aortic arteries using dedicated magnetic resonance imaging sequences.

Methods: Vessel wall and perivascular adipose tissue were acquired using magnetic resonance imaging (1.

Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction.

Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI). After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely. In humans, EV number correlated closely with the extent of myocardial injury.

Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans.

Aims: Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans.

Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: the regulatory role of perivascular adipose tissue.

Oxidative stress plays a critical role in the vascular complications of type 2 diabetes. We examined the effect of type 2 diabetes on NADPH oxidase in human vessels and explored the mechanisms of this interaction. Segments of internal mammary arteries (IMAs) with their perivascular adipose tissue (PVAT) and thoracic adipose tissue were obtained from 386 patients undergoing coronary bypass surgery (127 with type 2 diabetes).

Elevated blood pressure in preterm-born offspring associates with a distinct antiangiogenic state and microvascular abnormalities in adult life.

Preterm-born individuals have elevated blood pressure. We tested the hypothesis that this associates with an enhanced antiangiogenic circulating profile and that this association is mediated by variations in capillary density. We studied 204 adults aged 25 years (range, 20-30 years), of which 102 had been followed up prospectively since very preterm birth (mean gestational age, 30.

Are hearing losses among young Maori different to those found in the young NZ European population?

Aim: This study was undertaken to determine if young Maori have more permanent bilateral hearing loss, or less severe and profound hearing loss than New Zealand (NZ) Europeans.

Methods: Data include hearing-impaired children from birth to 19 years of age from the New Zealand Deafness Notification Database (DND) and covering the periods 1982-2005 and 2009-2013. These were retrospectively analysed, as was information on children and young people with cochlear implants.

Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease.

Objective: To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease.

Approach And Results: In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting.

Nicotinic acid receptor GPR109A is down-regulated in human macrophage-derived foam cells.

Nicotinic acid (NA) regresses atherosclerosis in human imaging studies and reduces atherosclerosis in mice, mediated by myeloid cells, independent of lipoproteins. Since GPR109A is expressed by human monocytes, we hypothesized that NA may drive cholesterol efflux from foam cells. In THP-1 cells NA suppressed LPS-induced mRNA transcription of MCP-1 by 76.

Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels.

Background: Adiponectin is an adipokine with potentially important roles in human cardiovascular disease states. We studied the role of adiponectin in the cross-talk between adipose tissue and vascular redox state in patients with atherosclerosis.

Methods And Results: The study included 677 patients undergoing coronary artery bypass graft surgery.

GPR109A and vascular inflammation.

GPR109A has generated expanding interest since its discovery as the receptor for niacin a decade ago, along with deorphanisation as the receptor for endogenous ligand 3-hydroxy-butyrate shortly after. This interest is generated especially because of the continuing exploration of niacin's "pleiotropic" mechanisms of action and its potential in the "cross-talk" between metabolic and inflammatory pathways. As GPR109A's primary pharmacological ligand in clinical use, niacin has been used for over 50 years in the treatment of cardiovascular disease, mainly due to its favourable effects on plasma lipoproteins.

Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus.

Rationale And Objective: Acute myocardial infarction (AMI) results in the recruitment of leukocytes to injured myocardium. Additionally, myocardium remote to the infarct zone also becomes inflamed and is associated with adverse left ventricular remodelling. Renal ischaemic syndromes have been associated with remote organ inflammation and impaired function.

Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms.

Objective: Nicotinic acid (NA) treatment has been associated with benefits in atherosclerosis that are usually attributed to effects on plasma lipoproteins. The NA receptor GPR109A is expressed in monocytes and macrophages, suggesting a possible additional role for NA in modulating function of these immune cells. We hypothesize that NA has the potential to act directly on monocytes to alter mediators of inflammation that may contribute to its antiatherogenic effects in vivo.

Niacin in cardiovascular disease: recent preclinical and clinical developments.

Niacin has been used for more than 50 years in the treatment of cardiovascular disease, although its use has largely been superseded by better-tolerated lipid-modulating interventions. There has been a renewed interest in the HDL-cholesterol raising properties of niacin, with the appreciation that substantial cardiovascular risk remains despite effective treatment of LDL-cholesterol. This coincides with increasing evidence that the complex functional properties of HDL are not well reflected by measurement of HDL-cholesterol alone.

Early diagnosis of perioperative myocardial infarction after coronary bypass grafting: a study using biomarkers and cardiac magnetic resonance imaging.

Background: Myocardial injury related to coronary artery bypass grafting (CABG) is poorly characterized, and understanding the characteristic release of biomarkers associated with revascularization injury might provide novel therapeutic opportunities. This study characterized early changes in biomarkers after revascularization injury during on-pump CABG.

Methods: This prospective study comprised 28 patients undergoing on-pump CABG and late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMRI) who underwent measurements of cardiac troponin I (cTnI), creatine kinase-MB, and inflammatory markers (C-reactive protein, serum amyloid A, myeloperoxidase, interleukin 6, tumor necrosis factor-α, matrix metalloproteinase 9a, monocyte chemotactic protein-1, plasminogen activator inhibitor-1a) at baseline, at 1, 6, 12, and 24 hours, and at 1 week (inflammatory markers only) post-CABG.

Molecular imaging with optical coherence tomography using ligand-conjugated microparticles that detect activated endothelial cells: rational design through target quantification.

Objectives: Optical coherence tomography (OCT) is a high resolution imaging technique used to assess superficial atherosclerotic plaque morphology. Utility of OCT may be enhanced by contrast agents targeting molecular mediators of inflammation.

Methods And Results: Microparticles of iron oxide (MPIO; 1 and 4.

Adiponectin (15-36) stimulates steroidogenic acute regulatory (StAR) protein expression and cortisol production in human adrenocortical cells: role of AMPK and MAPK kinase pathways.

Adiponectin is an abundantly circulating adipokine, orchestrating its effects through two 7-transmembrane receptors (AdipoR1 and AdipoR2). Steroidogenesis is regulated by a variety of neuropeptides and adipokines. Earlier studies have reported adipokine mediated steroid production.

With the "universal definition," measurement of creatine kinase-myocardial band rather than troponin allows more accurate diagnosis of periprocedural necrosis and infarction after coronary intervention.

Objectives: We aimed to assess the differential implications of creatine kinase-myocardial band (CK-MB) and troponin measurement with the universal definition of periprocedural injury after percutaneous coronary intervention.

Background: Differentiation between definitions of periprocedural necrosis and periprocedural infarction has practical, sociological, and research implications. Troponin is the recommended biomarker, but there has been debate about the recommended diagnostic thresholds.

Effects of niacin on atherosclerosis and vascular function.

Purpose Of Review: Niacin has been used for more than 50 years in the management of atherosclerosis and is associated with improved patient outcomes. The routine use of niacin has been superseded in recent years with the advent of newer lipid-modulating interventions. Recently, however, there has been a renewed interest in its use due to the appreciation of its many beneficial effects on atherosclerosis and endothelial function, both 'lipid-targeted' and 'pleiotropic'.

Brachial artery low-flow-mediated constriction is increased early after coronary intervention and reduces during recovery after acute coronary syndrome: characterization of a recently described index of vascular function.

Aims: The endothelium plays a role in regulating vascular tone. Acute and dynamic changes in low-flow-mediated constriction (L-FMC) and how it changes with regard to traditional flow-mediated dilatation (FMD) have not been described. We aimed to investigate the changes in brachial artery L-FMC following percutaneous coronary intervention (PCI) and during recovery from non-ST-segment elevation myocardial infarction (NSTEMI).

In vivo quantification of VCAM-1 expression in renal ischemia reperfusion injury using non-invasive magnetic resonance molecular imaging.

Rationale And Objective: Vascular cell adhesion molecule-1 (VCAM-1) is upregulated in ischemia reperfusion injury (IRI), persisting after restoration of blood flow. We hypothesized that microparticles of iron oxide targeting VCAM-1 (VCAM-MPIO) would depict "ischemic memory" and enable in vivo assessment of VCAM-1 expression.

Methodology And Findings: Mice subject to unilateral, transient (30 minutes) renal ischemia and subsequent reperfusion received intravenous VCAM-MPIO (4.

Reduced negative surface charge on arterial endothelium explains accelerated atherosclerosis in type 2 diabetic patients.

Reduced endothelial surface charge markedly increases the rate of LDL uptake into blood vessels. Previous work in the streptozotocin diabetic rat reported reduced endothelial surface charge. We compared endothelial surface charge density in internal mammary artery rings from patients with type 2 diabetes (n = 12) and from non diabetic patients undergoing coronary artery bypass grafting, and observed a substantial (52%) reduction in the former.

Regulation of beta-cell viability and gene expression by distinct agonist fragments of adiponectin.

Obesity is an established risk factor for type 2 diabetes. Activation of the adiponectin receptors has a clear role in improving insulin resistance although conflicting evidence exists for its effects on pancreatic beta-cells. Previous reports have identified both adiponectin receptors (ADR-1 and ADR-2) in the beta-cell.