A Multiplexed Quantitative Proteomics Approach to the Human Plasma Protein Signature.

Despite the plasma proteome being able to provide a unique insight into the health and disease status of individuals, holding singular promise as a source of protein biomarkers that could be pivotal in the context of personalized medicine, only around 100 proteins covering a few human conditions have been approved as biomarkers by the US Food and Drug Administration (FDA) so far. Mass spectrometry (MS) currently has enormous potential for high-throughput analysis in clinical research; however, plasma proteomics remains challenging mainly due to the wide dynamic range of plasma protein abundances and the time-consuming procedures required. We applied a new MS-based multiplexed proteomics workflow to quantitate proteins, encompassing 67 FDA-approved biomarkers, in >1300 human plasma samples from a clinical cohort.

Role of LCN2 in a murine model of hindlimb ischemia and in peripheral artery disease patients, and its potential regulation by miR-138-5P.

Background And Aims: Peripheral arterial disease (PAD) is a leading cause of morbimortality worldwide. Lipocalin-2 (LCN2) has been associated with higher risk of amputation or mortality in PAD and might be involved in muscle regeneration. Our aim is to unravel the role of LCN2 in skeletal muscle repair and PAD.

B- and T-lymphocyte attenuator could be a new player in accelerated atherosclerosis associated with chronic kidney disease.

Background: In chronic kidney disease (CKD), cardiovascular morbi-mortality is higher than in general population. Atherosclerotic cardiovascular disease is accelerated in CKD, but specific CKD-related risk factors for atherosclerosis are unknown.

Methods: CKD patients from the NEFRONA study were used.

The presence of activating IgG Fc receptors in macrophages aggravates the development of experimental abdominal aortic aneurysm.

Introduction: Abdominal aortic aneurysm (AAA) is a multifactorial, degenerative disease characterized by progressive aortic dilation and chronic activation of inflammation, proteolytic activity, and oxidative stress in the aortic wall. The immune response triggered by antibodies against antigens present in the vascular wall participates in the formation and progression of AAA through mechanisms not completely understood. This work analyses the function of specific IgG receptors (FcγR), especially those expressed by monocytes/macrophages, in the development of experimental AAA.

Implication of miR-155-5p and miR-143-3p in the Vascular Insulin Resistance and Instability of Human and Experimental Atherosclerotic Plaque.

(1) Background: Cardiovascular diseases (CVDs) are the main cause of death in developed countries, being atherosclerosis, a recurring process underlying their apparition. MicroRNAs (miRNAs) modulate the expression of their targets and have emerged as key players in CVDs; (2) Methods: 18 miRNAs were selected (Pubmed and GEO database) for their possible role in promoting atherosclerosis and were analysed by RT-qPCR in the aorta from apolipoprotein E-deficient () mice. Afterwards, the altered miRNAs in the aorta from 18 weeks- mice were studied in human aortic and carotid samples; (3) Results: miR-155-5p was overexpressed and miR-143-3p was downregulated in mouse and human atherosclerotic lesions.

NT-proBNP Levels Influence the Prognostic Value of Mineral Metabolism Biomarkers in Coronary Artery Disease.

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet.

Rewiring Vascular Metabolism Prevents Sudden Death due to Aortic Ruptures-Brief Report.

Background: The goal of this study was to determine whether boosting mitochondrial respiration prevents the development of fatal aortic ruptures triggered by atherosclerosis and hypertension.

Methods: Ang-II (angiotensin-II) was infused in ApoE (Apolipoprotein E)-deficient mice fed with a western diet to induce acute aortic aneurysms and lethal ruptures.

Results: We found decreased mitochondrial respiration and mitochondrial proteins in vascular smooth muscle cells from murine and human aortic aneurysms.

Role of Extracellular Vesicles as Potential Diagnostic and/or Therapeutic Biomarkers in Chronic Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the first cause of death worldwide. In recent years, there has been great interest in the analysis of extracellular vesicles (EVs), including exosomes and microparticles, as potential mediators of biological communication between circulating cells/plasma and cells of the vasculature. Besides their activity as biological effectors, EVs have been also investigated as circulating/systemic biomarkers in different acute and chronic CVDs.

Unbiased plasma proteomics discovery of biomarkers for improved detection of subclinical atherosclerosis.

Background: Imaging of subclinical atherosclerosis improves cardiovascular risk prediction on top of traditional risk factors. However, cardiovascular imaging is not universally available. This work aims to identify circulating proteins that could predict subclinical atherosclerosis.

Impact of renal function on the prognostic value of mineral metabolism in patients with chronic ischaemic heart disease patients with chronic ischaemic heart disease.

Background: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts.

N-Terminal Pro-Brain Natriuretic Peptide Plasma Levels Are Associated with Intermediate-Term Follow-Up Cancer in Coronary Patients.

N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper, we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the intermediate-term follow-up. We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline.

Fcγ receptor activation mediates vascular inflammation and abdominal aortic aneurysm development.

Background: Abdominal aortic aneurysm (AAA), a degenerative vascular pathology characterized by permanent dilation of the aorta, is considered a chronic inflammatory disease involving innate/adaptive immunity. However, the functional role of antibody-dependent immune response against antigens present in the damaged vessel remains unresolved. We hypothesized that engagement of immunoglobulin G (IgG) Fc receptors (FcγR) by immune complexes (IC) in the aortic wall contributes to AAA development.

Parathormone levels add prognostic ability to N-terminal pro-brain natriuretic peptide in stable coronary patients.

Aims: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers.

Methods And Results: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein.

MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation.

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.

Extracellular Tuning of Mitochondrial Respiration Leads to Aortic Aneurysm.

Background: Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the (fibrillin-1) gene encoding a large glycoprotein in the extracellular matrix called fibrillin-1. The major complication of this connective disorder is the risk to develop thoracic aortic aneurysm. To date, no effective pharmacologic therapies have been identified for the management of thoracic aortic disease and the only options capable of preventing aneurysm rupture are endovascular repair or open surgery.

Annexins: Involvement in cholesterol homeostasis, inflammatory response and atherosclerosis.

The annexin superfamily consists of 12 proteins with a highly structural homology that binds to phospholipids depending on the availability of Ca-dependent. Different studies of overexpression, inhibition, or using recombinant proteins have linked the main function of these proteins to their dynamic and reversible binding to membranes. Annexins are found in multiple cellular compartments, regulating different functions, such as membrane trafficking, anchoring to the cell cytoskeleton, ion channel regulation, as well as pro- or anti-inflammatory and anticoagulant activities.

Protective effect of suppressor of cytokine signalling 1-based therapy in experimental abdominal aortic aneurysm.

Background And Purpose: Abdominal aortic aneurysm (AAA) is a multifactorial disease characterized by chronic inflammation, oxidative stress and proteolytic activity in the aortic wall. Targeting JAK/signal transducer and activator of transcription (JAK/STAT) pathway is a promising strategy for chronic inflammatory diseases. We investigated the vasculo-protective role of suppressor of cytokine signalling-1 (SOCS1), the negative JAK/STAT regulator, in experimental AAA.

Monocyte Chemoattractant Protein-1 Is an Independent Predictor of Coronary Artery Ectasia in Patients with Acute Coronary Syndrome.

Our purpose was to assess a possible association of inflammatory, lipid and mineral metabolism biomarkers with coronary artery ectasia (CAE) and to determine a possible association of this with acute atherotrombotic events (AAT). We studied 270 patients who underwent coronary angiography during an acute coronary syndrome 6 months before. Plasma levels of several biomarkers were assessed, and patients were followed during a median of 5.

Red Blood Cells and Hemoglobin in Human Atherosclerosis and Related Arterial Diseases.

As the main particulate component of the circulating blood, RBCs play major roles in physiological hemodynamics and impact all arterial wall pathologies. RBCs are the main determinant of blood viscosity, defining the frictional forces exerted by the blood on the arterial wall. This function is used in phylogeny and ontogeny of the cardiovascular (CV) system, allowing the acquisition of vasomotricity adapted to local metabolic demands, and systemic arterial pressure after birth.

Macrophage Cholesterol Efflux Downregulation Is Not Associated with Abdominal Aortic Aneurysm (AAA) Progression.

Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients (aortic diameter between 30 and 50 mm) and 38 control subjects (aortic diameter < 30 mm). We evaluated the potential of HDL-mediated macrophage cholesterol efflux (MCE) to predict AAA growth and/or the need for surgery.

Complement C5 Protein as a Marker of Subclinical Atherosclerosis.

Background: The mechanisms underlying early atherosclerotic plaque formation are not completely understood. Moreover, plasma biomarkers of subclinical atherosclerosis are lacking.

Objectives: The purpose of this study was to analyze the temporal and topologically resolved protein changes taking place in human aortas with early atherosclerosis to find new potential diagnostic and/or therapeutic targets.

IgG Anti-High Density Lipoprotein Antibodies Are Elevated in Abdominal Aortic Aneurysm and Associated with Lipid Profile and Clinical Features.

High-density lipoproteins cholesterol (HDLc) levels are decreased in abdominal aortic aneurysm (AAA), which is hallmarked by autoimmunity and lipid aortic deposits. To investigate whether IgG anti-HDL antibodies were present in AAA and their potential association with clinical features, IgG anti-HDL and total IgG along with HDLc plasma levels were measured in 488 AAA patients and 184 controls from the Viborg Vascular (VIVA) study, and in tissue-conditioned media from AAA intraluminal thrombus and media layer samples compared to control aortas. Higher IgG anti-HDL levels were found in AAA compared to controls, even after correcting for total IgG, and after adjusting for potential confounders.

Role of complement system in pathological remodeling of the vascular wall.

Cardiovascular diseases (CVD) remain the major cause of morbidity and mortality in Europe. The clinical complications associated to arterial wall rupture involve intimal cap rupture in complicated atherosclerotic plaques and medial rupture in abdominal aortic aneurysm (AAA). The mechanisms underlying pathological vascular remodeling include lipid accumulation, cell proliferation, redox imbalance, proteolysis, leukocyte infiltration, cell death, and eventually, thrombosis.