Cysteine-rich with EGF-like domains 2 (CRELD2) is an endoplasmic reticulum stress-inducible angiogenic growth factor promoting ischemic heart repair.

Tissue repair after myocardial infarction (MI) is guided by autocrine and paracrine-acting proteins. Deciphering these signals and their upstream triggers is essential when considering infarct healing as a therapeutic target. Here we perform a bioinformatic secretome analysis in mouse cardiac endothelial cells and identify cysteine-rich with EGF-like domains 2 (CRELD2), an endoplasmic reticulum stress-inducible protein with poorly characterized function.

Molecular Imaging of Myocardial Fibroblast Activation in Patients with Advanced Aortic Stenosis Before Transcatheter Aortic Valve Replacement: A Pilot Study.

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity.

Circulating fibroblast activation protein α is reduced in acute ischemic stroke.

Background: Fibroblast activation protein α (FAP), a membrane glycoprotein with dipeptidyl-peptidase and collagenase properties, is expressed in atherosclerotic plaques and remodeling of the extracellular matrix based on fibrosis. Fibrosis is a main contributor of atrial cardiomyopathies. In acute MI, circulating FAP is associated with outcome.

Cardiac Fibroblast Activation in Patients Early After Acute Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome.

After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Thirty-five patients underwent CMR, perfusion SPECT, and Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI.

[Uncommon tumor-associated deep vein thrombosis].

Here, we report on a patient with deep vein thrombosis of the right leg, in whom diagnostic work-up revealed a previously unknown chondrosarcoma of the tibia. Physical examination revealed a firm, nondisplaceable mass on the dorsal side of the right knee that appeared as a cystic formation on ultrasound. X‑ray, computed tomography, and magnetic resonance imaging were consistent with chondrosarcoma, which had likely provoked the thrombosis by local compression or paraneoplastic mechanisms.

Molecular imaging of fibroblast activation protein after myocardial infarction using the novel radiotracer [Ga]MHLL1.

Myocardial infarction (MI) evokes an organized remodeling process characterized by the activation and transdifferentiation of quiescent cardiac fibroblasts to generate a stable collagen rich scar. Early fibroblast activation may be amenable to targeted therapy, but is challenging to identify . We aimed to non-invasively image active fibrosis by targeting the fibroblast activation protein (FAP) expressed by activated (myo)fibroblasts, using a novel positron emission tomography (PET) radioligand [Ga]MHLL1 after acute MI.

Genetic ablation of fibroblast activation protein alpha attenuates left ventricular dilation after myocardial infarction.

Introduction: Regulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI.

Plasma Concentrations of Myeloid-Derived Growth Factor in Healthy Individuals and Patients with Acute Myocardial Infarction as Assessed by Multiple Reaction Monitoring-Mass Spectrometry.

Myeloid-derived growth factor (MYDGF in humans, Mydgf in mice) is a secreted protein with previously unknown biological functions. In a recent study, Mydgf was shown to mediate cardiac repair after acute myocardial infarction (MI) in mice. Lack of a sensitive assay to measure MYDGF in the circulation has hampered its further investigation.

One-year outcomes with the HeartMate 3 left ventricular assist device.

Background: The HeartMate 3 (HM3; Abbott Laboratories, Lake Forest, Ill) left ventricular assist device (LVAD) received its Conformité Européenne mark for Europe in October 2015 and is currently under investigation of the Food and Drug Administration to gain approval in the United States. Within this study, we present the first real-world experiences, 1-year outcomes, and adverse events of a single-center cohort treated with the HM3.

Methods: We prospectively studied midterm results of 27 consecutive patients receiving the HM3 at a single institution.

Changes in concentrations of circulating fibroblast activation protein alpha are associated with myocardial damage in patients with acute ST-elevation MI.

Background: Fibroblast activation protein alpha (FAP) is a membrane-bound serine protease expressed by activated fibroblasts after myocardial infarction (MI). Reduced circulating FAP levels were associated with increased mortality in patients with acute coronary syndrome. We hypothesized that FAP concentrations are altered after acute ST-elevation MI (STEMI), and related to myocardial damage.

Efficacy of prasugrel administration immediately after percutaneous coronary intervention in ST-elevation myocardial infarction.

Prasugrel, a potent thienopyridine, achieves stronger inhibition of platelet activation than clopidogrel. However, onset of inhibition is significantly delayed in patients with acute ST-elevation myocardial infarction (STEMI), as haemodynamic instability and morphine application seem to exhibit significant influence. Since rapid onset of effect was demonstrated in non-STEMI patients when prasugrel was administered only after percutaneous coronary intervention (PCI) without increasing cardiovascular event rates we assessed the efficacy of prasugrel loading immediately after PCI for STEMI instead of pre-loading before revascularisation.

Molecular Imaging of the Chemokine Receptor CXCR4 After Acute Myocardial Infarction.

Objectives: An assay for molecular imaging of myocardial CXCR4 expression was evaluated, in order to obtain mechanistic insights noninvasively based on quantitative positron emission tomography (PET).

Background: The chemokine receptor CXCR4 has emerged as a therapeutic target after acute myocardial infarction (AMI), because of its role in inflammatory and progenitor cell recruitment.

Methods: PET with the specific CXCR4 ligand, gallium-68 ((68)Ga)-pentixafor, was performed in mice (n = 53) and compared with ex vivo autoradiography, immunohistochemistry, and left ventricular flow cytometry.

Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction.

Introduction: Fibroblast activation protein α (FAP) is a membrane-bound serine protease expressed by activated fibroblasts during wound healing in the skin. Expression of FAP after myocardial infarction (MI) and potential effects on cardiac wound healing are largely unknown.

Methods: MI was induced in rats and FAP expression was analyzed at 3, 7 and 28 days post-MI by microarray, Western blot and immunohistochemistry.

PET imaging of cardiac wound healing using a novel [68Ga]-labeled NGR probe in rat myocardial infarction.

Purpose: Peptides containing the asparagine-glycine-arginine (NGR) motif bind to aminopeptidase N (CD13), which is expressed on inflammatory cells, endothelial cells, and fibroblasts. It is unclear whether radiolabeled NGR-containing tracers could be used for in vivo imaging of the early wound-healing phase after myocardial infarction (MI) using positron emission tomography (PET).

Procedures: Uptake of novel tracer [(68)Ga]NGR was assessed together with [(68)Ga]arginine-glycine-aspartic acid ([(68)Ga]RGD) and 2-deoxy-2-[(18) F]fluoro-D-glucose after myocardial ischemia/reperfusion (MI/R) injury using μ-PET and autoradiography, and relative expressions of CD13 and integrin β3 were assessed in fibroblasts, inflammatory cells, and endothelial cells by immunohistochemistry.

Circulating concentrations of fibroblast activation protein α in apparently healthy individuals and patients with acute coronary syndrome as assessed by sandwich ELISA.

Background: Fibroblast activation protein α (FAP) is a membrane glycoprotein with dipeptidyl-peptidase and collagenase activity and is expressed in cancer, arthritis, and atherosclerotic plaques. We hypothesized that FAP can be measured quantitatively in the circulation and provide prognostic information in acute coronary syndrome (ACS).

Methods: We assessed the performance of a commercially available FAP ELISA and the pre-analytic characteristics of the marker.

Impact of different bone marrow cell preparations on left ventricular remodelling after experimental myocardial infarction.

Objective: Bone marrow (BM)-derived haematopoietic stem cells have been proposed as a potential cell source to functionally engraft the myocardium and to improve cardiac function after myocardial infarction (MI). However, experimental and clinical data are inconsistent. Since the specific characteristics of different BM cell subsets could influence their therapeutic potential we determined the effect of different BM cell populations on left ventricular remodelling after MI.

Formation of large coronary arteries by cardiac progenitor cells.

Coronary artery disease is the most common cause of cardiac failure in the Western world, and to date there is no alternative to bypass surgery for severe coronary atherosclerosis. We report that c-kit-positive cardiac progenitor cells (CPCs) activated with insulin-like growth factor 1 and hepatocyte growth factor before their injection in proximity of the site of occlusion of the left coronary artery in rats, engrafted within the host myocardium forming temporary niches. Subsequently, CPCs divided and differentiated into endothelial cells and smooth muscle cells and, to a lesser extent, into cardiomyocytes.

Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan.

Heart failure is the leading cause of death in the elderly, but whether this is the result of a primary aging myopathy dictated by depletion of the cardiac progenitor cell (CPC) pool is unknown. Similarly, whether current lifespan reflects the ineluctable genetic clock or heart failure interferes with the genetically determined fate of the organ and organism is an important question. We have identified that chronological age leads to telomeric shortening in CPCs, which by necessity generate a differentiated progeny that rapidly acquires the senescent phenotype conditioning organ aging.

Human cardiac stem cells.

The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium.

The young mouse heart is composed of myocytes heterogeneous in age and function.

The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16(INK4a) and telomere length.

Tissue-specific effects of the nuclear factor kappaB subunit p50 on myocardial ischemia-reperfusion injury.

Nuclear factor kappaB (NF-kappaB) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-kappaB in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-kappaB subunit p50.