Glutaredoxin-1 levels in plasma can predict future events in patients with cardiovascular diseases.

Reactive oxygen species that increase during cardiovascular disease (CVD) react with protein cysteine residues to form a glutathione adduct by S-glutathionylation, which is selectively removed by glutaredoxin-1 (Glrx). We previously showed that S-glutathionylation and Glrx play important roles in mouse models of CVD, such as heart failure and peripheral artery disease models. However, there are few clinical studies on Glrx in CVD.

Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with myocardial infarction.

Background: Renal dysfunction, defined as a lower estimated glomerular filtration rate (eGFR), has been shown to be related to cardiovascular events in patients with myocardial infarction (MI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of cardiac death and recurrence of MI in patients who have had MI.

Group V Secretory Phospholipase A Regulates Endocytosis of Acetylated LDL by Transcriptional Activation of PGK1 in RAW264.7 Macrophage Cell Line.

Aims: It was suggested that group V secretory phospholipase A (sPLA-V) existed in the nucleus. This study examined whether nuclear sPLA-V plays a role in endocytosis of acetylated low-density lipoprotein (AcLDL) in monocyte/macrophage-like cell line RAW264.7 cells.

Persistent Myocardial Production of Follistatin-like 1 Is Associated With Left Ventricular Adverse Remodeling in Patients With Myocardial Infarction: Myocardial production of FSTL1 in AMI patients.

Background: Although animal studies showed that Follistatin-like 1 (FSTL1) exerts cardioprotective effects against ischemic injury, little is known in humans. We examined whether FSTL1 is secreted in an infarcted myocardium and whether its production is associated with left ventricular (LV) remodeling in survivors of acute myocardial infarction.

Methods And Results: FSTL1 levels were measured by enzyme-linked immunosorbent assay in plasma collected from the aortic root and the anterior interventricular vein in 93 patients with anterior acute myocardial infarction.

Protein S-glutathionylation stimulate adipogenesis by stabilizing C/EBPβ in 3T3L1 cells.

Reactive oxygen species (ROS) increase during adipogenesis and in obesity. Oxidants react with cysteine residues of proteins to form glutathione (GSH) adducts, S-glutathionylation, that are selectively removed by glutaredoxin-1 (Glrx). We have previously reported that Glrx knockout mice had increased protein S-glutathionylation and developed obesity by an unknown mechanism.

Deficiency of Phospholipase A Receptor Exacerbates Autoimmune Myocarditis in Mice.

Secretory phospholipase A (sPLA) plays a critical role in the pathogenesis of various inflammatory diseases through production of pro-inflammatory eicosanoids. PLA receptor 1 (PLAR) acts as a clearance receptor for sPLAs. This study examined whether PLAR plays a role in the pathogenesis of experimental autoimmune myocarditis using PLAR-deficient (PLAR KO) mice on a BALB/c background.

Persistent Dysfunction of Coronary Endothelial Vasomotor Responses is Related to Atheroma Plaque Progression in the Infarct-Related Coronary Artery of AMI Survivors.

Aim: Although coronary endothelial vasomotor dysfunction predicts future coronary events, there are few human studies showing the relationship between endothelial vasomotor dysfunction and atheroma plaque progression in the same coronary artery. This study examined whether endothelial vasomotor dysfunction is related to atheroma plaque progression in the infarct-related coronary artery of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessment of coronary plaque size with intravascular ultrasound (IVUS) and coronary vasomotor responses to acetylcholine (ACh).

Methods: This study included 50 patients with a first acute STEMI due to occlusion of the left anterior descending coronary artery (LAD) and successful reperfusion therapy with percutaneous coronary intervention (PCI).

Remnant Lipoproteins Are Residual Risk Factor for Future Cardiovascular Events in Patients With Stable Coronary Artery Disease and On-Statin Low-Density Lipoprotein Cholesterol Levels <70 mg/dL.

Background: This study examined the predictive value of remnant lipoprotein levels for cardiovascular events (CVEs) in patients with stable coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) levels <70 mg/dL on statin treatment.

Methods and results: Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol: RLP-C) were measured by an immunoseparation method in 247 consecutive patients with CAD who had on-statin LDL-C levels <70 mg/dL. All the patients were followed prospectively for a period of ≤60 months or until the occurrence of the primary composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, worsening heart failure, peripheral artery disease, aortic event, and ischemic stroke.

High levels of stromal cell-derived factor-1α predict short-term progression of renal dysfunction in patients with coronary artery disease.

Background: Stromal cell-derived factor-1α (SDF-1α) is an inflammatory chemokine that plays a critical role in cardiovascular disease. Although persistent inflammation causes renal dysfunction, it remains unclear whether SDF-1α is related to progression of chronic kidney disease. This study examined whether high levels of SDF-1α are associated with future declines in renal function in patients with coronary artery disease (CAD).

Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Background: The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF.

Human soluble phospholipase A receptor is an inhibitor of the integrin-mediated cell migratory response to collagen-I.

Murine membrane-bound phospholipase A receptor 1 (PLAR) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLAR. This study examined whether human soluble PLAR has biological functions and whether soluble PLAR exists in human plasma.

Effect of coronary artery spasm on long-term outcomes in survivors of acute myocardial infarction.

Background: The prevalence of coronary artery spasm (CAS) inducible by intracoronary injection of acetylcholine (ACh) is high in survivors of acute myocardial infarction (AMI). Although there is a potential risk of sudden cardiac death in patients with CAS, the prognostic value of CAS was not clear. Thus, this study examined the effect of CAS on long-term prognosis in survivors of AMI in a prospective manner.

Angiotensin II receptor blockers suppress the release of stromal cell-derived factor-1α from infarcted myocardium in patients with acute myocardial infarction.

Background: Although angiotensin II receptor blockers (ARBs) have been shown to have anti-inflammatory effects on infarcted myocardium in experimental models, little is known in humans. Stromal cell-derived factor-1α (SDF-1α), a pro-inflammatory chemokine, is released from infarcted tissue in patients with acute myocardial infarction (AMI). This study examined whether ARBs suppress SDF-1α production in the infarcted lesion in patients with AMI.

Echolucency of the carotid artery is associated with short-term plaque progression and positive remodeling in the culprit coronary artery in AMI survivors.

Background: Rapid plaque progression and positive remodeling are recognized as vulnerable coronary plaque characteristics. This study examined whether serial carotid ultrasonography might be of value for assessment of coronary plaque progression and positive remodeling, measured by serial intravascular ultrasound (IVUS), in survivors of acute myocardial infarction (AMI).

Methods: Thirty-nine patients with AMI had repeated examinations by IVUS of culprit coronary arteries and echolucency of the coronary artery on admission (1st test) and 6 months later (2nd test).

High levels of stromal cell-derived factor-1α predict secondary cardiac events in stable patients with a history of myocardial infarction.

Background: We recently showed that stromal cell-derived factor (SDF)-1α, a pro-inflammatory mediator, is produced in infarcted myocardium and is associated with left ventricular (LV) adverse remodeling and progressive dysfunction following acute myocardial infarction (AMI). The current study examined whether SDF-1α levels in the peripheral vein can provide prognostic information of outcomes in stable patients with a history of MI.

Methods: Plasma levels of SDF-1α in the peripheral vein were measured by enzyme-linked immunosorbent assay in 192 stable patients with a history of MI.

Remnant lipoproteinemia predicts cardiovascular events in patients with type 2 diabetes and chronic kidney disease.

Background: Patients having type 2 diabetes mellitus (DM) and chronic kidney disease (CKD) are at high risk of cardiovascular events. Triglyceride-rich lipoprotein levels are synergistically increased in patients with DM and CKD. This study examined the predictive value of remnant lipoprotein levels for cardiovascular events in patients with DM and CKD.

Phospholipase A Receptor Gene Polymorphisms Alter its Functions and Present a Genetic Risk of an Increased Intima-Media Thickness of the Carotid Artery.

Aims: Phospholipase A receptor 1 (PLAR) has multiple biological functions other than functioning as a receptor for secretory PLAs. Two nonsynonymous polymorphisms in the C-type lectin-like domains (CTLD) 1 of PLAR gene have been associated with idiopathic membranous nephropathy. This study examined whether the same PLAR polymorphisms may alter functions of PLAR in cells expressing the variant PLAR.

Myocardial Production of Plasminogen Activator Inhibitor-1 is Associated with Coronary Endothelial and Ventricular Dysfunction after Acute Myocardial Infarction.

Aim: Although plasminogen activator inhibitor-1 (PAI-1) is abundantly expressed in infarcted myocardium, the pathogenic role of myocardial PAI-1 remains unknown. This study examined whether PAI-1 in the infarcted lesion contributes to coronary endothelial dysfunction and left ventricular (LV) dysfunction in patients with acute myocardial infarction (AMI).

Methods: Plasma levels of PAI-1 activity and tissue-plasminogen activator (tPA) antigen were measured 2 weeks and 6 months after MI by ELISA in plasma obtained from the aortic root (AO) and anterior interventricular vein (AIV) in 28 patients with a first AMI due to occlusion of the left anterior descending coronary artery (LAD).

Sustained myocardial production of stromal cell-derived factor-1α was associated with left ventricular adverse remodeling in patients with myocardial infarction.

The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI.

Assessment of carotid plaque neovascularization using quantitative analysis of contrast-enhanced ultrasound imaging is useful for risk stratification in patients with coronary artery disease.

Background: Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization, a feature of unstable atherosclerotic plaques. This study examined whether assessment of intra-plaque neovascularization of the carotid artery using CEUS provides prognostic information in patients with coronary artery disease (CAD).

Methods: A total of 206 patients with stable CAD underwent a CEUS examination of the carotid artery and were followed up prospectively for <38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (uAP) requiring unplanned coronary revascularization, or heart failure requiring hospitalization).

Echolucent Carotid Plaque is Associated with Future Renal Dysfunction in Patients with Stable Coronary Artery Disease.

Aim: Functional and structural abnormalities of the peripheral arteries are associated with renal dysfunction, independent of the presence of renal artery stenosis. This study investigated whether echolucent carotid plaque is associated with a future decline in the renal function in patients with coronary artery disease (CAD).

Methods: Ultrasound assessments of carotid plaque echolucency with integrated backscatter (IBS) analyses were performed in 327 patients with stable CAD and carotid plaque who exhibited a normal renal function (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.

C-type lectin-like domain and fibronectin-like type II domain of phospholipase A(2) receptor 1 modulate binding and migratory responses to collagen.

Phospholipase A2 receptor 1 (PLA2R) mediates collagen-dependent migration. The mechanisms by which PLA2R interacts with collagen remain unclear. We produced HEK293 cells expressing full-length wild-type PLA2R or a truncated PLA2R that lacks fibronectin-like type II (FNII) domains or several regions of C-type lectin-like domain (CTLD).

The expression of groups IIE and V phospholipase A2 is associated with an increased expression of osteogenic molecules in human calcified aortic valves.

Aim: Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues.

Combined assessment of flow-mediated dilation of the brachial artery and brachial-ankle pulse wave velocity improves the prediction of future coronary events in patients with chronic coronary artery disease.

Background And Purpose: Measurement of either flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery, brachial-ankle pulse wave velocity (baPWV), or intima-media thickness (IMT) of the carotid artery is useful for risk assessment of future cardiovascular events. This study examined whether combination of these vascular parameters may have an additive effect on the ability of traditional risk factors to predict coronary events in patients with chronic coronary artery disease (CAD).

Methods: Patients (n=923) with stable CAD had measurements of FMD, baPWV, and maximum IMT (maxIMT), and were prospectively followed up for <8.

Lack of phospholipase A2 receptor increases susceptibility to cardiac rupture after myocardial infarction.

Rationale: Recent evidence indicates that the biological effects of secretory phospholipase A2 (sPLA2) cannot be fully explained by its catalytic activity. A cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high-affinity ligands (including sPLA2-IB, sPLA2-IIE, and sPLA2-X) are expressed in the infarcted myocardium.

Objective: This study asked whether PLA2R might play a pathogenic role in myocardial infarction (MI) using mice lacking PLA2R (PLA2R(-/-)).