Joseph B Moore IV

University of Louisville | UL · Center for Cardiometabolic Science

Intrinsic cardiogenic factor expression, a proxy for cardiomyogenic lineage commitment, may be an important determinant of donor cell cardiac reparative capacity in cell therapy applications; however, whether and how this contributes to their salutary effects remain largely ambiguous. Methods: The current study examined the consequences of enhanced...

The recent emergence of epitranscriptomics, a field of study that examines RNA modifications, provides a potential avenue for identifying interlinked mechanisms of cardiomyocyte survival and death. To date, over 140 RNA modifications have been identified; these modifications appear important because they can affect the fate of RNAs, including their...

The cardiac extracellular matrix plays essential roles in homeostasis and injury responses. Although the role of fibrillar collagens have been thoroughly documented, the functions of non-fibrillar collagen members remain underexplored. These include a distinct group of non-fibrillar collagens, termed, fibril-associated collagens with interrupted tr...

Scientific advancement is predicated upon the ability of a novel discovery to be independently reproduced and substantiated by others. Despite this inherent necessity, the research community is awash in published studies that cannot be replicated resulting in widespread confusion within the field and waning trust from the general public. In many ca...

Introduction: Branch-chain amino acids (BCAAs) are markedly elevated in the heart following myocardial infarction (MI) in both humans and animal models. Nevertheless, it remains unclear whether dietary BCAA levels influence post-MI remodeling. We hypothesize that lowering dietary BCAA levels prevents adverse cardiac remodeling after MI. Methods and...

Background Abdominal aortic aneurysms (AAA) are characterized by loss of vascular smooth muscle cells (SMCs) and extracellular matrix (ECM) degradation. The catalytic PI 3-kinase isoform p110α signals downstream of growth factor receptors. Mice harboring an SMC-specific p110α deficiency (SM-p110α-/-) are characterized by impaired SMC proliferation...

Introduction: Collagen deposition is required for repair of the heart following myocardial infarction (MI). As collagen abundance increases, so does its alignment, potentially influencing scar integrity. Because cell-matrix interactions regulate fibroblast behavior and matrix dynamics, adhesive factors, like cellular communication network (CCN) pro...

word count: 344 24 Total number of figures and tables: 7/1 25 Total number of online figures and tables: 5/2 Abstract 55 Rationale: Aortic valve stenosis (AVS) is a major contributor to cardiovascular death in the elderly population

Background: Catalytic class IA PI 3-kinase isoform p110alpha is a crucial regulator of cellular proliferation and survival in numerous cell types. While p110alpha is critically involved in pathogenic vascular remodeling, its physiological role for vascular integrity under stress conditions has not been studied. We report a protective function of sm...

Rationale Aortic valve stenosis (AVS) is a major contributor to cardiovascular death in the elderly population worldwide. MicroRNAs (miRNAs) are highly dysregulated in patients with AVS undergoing surgical aortic valve replacement (SAVR). However, miRNA-dependent mechanisms regulating inflammation and calcification or miRNA-mediated cell-cell cross...

Introduction: Cellular communication network (CCN) proteins constitute a 6-member family of extracellular matrix (ECM)-associated signaling proteins that have important roles in wound healing and tissue fibrosis. Though their function in the heart is not fully explicated, CCN1 is often indicated as an antifibrotic factor. Yet, CCN1 levels correlate...

Transcatheter aortic valve replacement is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic AVS. However, a specific role for circulating microRNAs in the improvement of cardiac function for patients after TAVR has not yet been investigated. Methods: Circulating EV-associated miRNAs were investigat...

Despite entering an endemic phase, SARS-CoV-2 remains a significant burden to public health across the global community. Wastewater sampling has consistently proven utility to understanding SARS-CoV-2 prevalence trends and genetic variation as it represents a less biased assessment of the corresponding communities. Here, we report that ongoing moni...

Background Proliferation and phenotypic modulation of vascular smooth muscle cells (SMCs) significantly contribute to the functionality of the aortic wall. Dysregulation of underlying signal transduction pathways impairs the vessel wall structure and promote the development and progression of abdominal aortic aneurysms (AAA). The PI 3-kinase (PI3K)...

This study aimed to develop a framework for combining community wastewater surveillance with state clinical surveillance for the confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants within the community and to provide recommendations on how to expand on such research and apply the findings in public health responses...

Excitable cells of the nervous and cardiovascular systems depend on an assortment of plasmalemmal potassium channels to control diverse cellular functions. Voltage-gated potassium (Kv) channels are central to the feedback control of membrane excitability in these processes due to their activation by depolarized membrane potentials permitting K+ eff...

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic aortic valve stenosis. A majority of patients exhibit improvements in left ventricular ejection fraction (LVEF) after TAVR in response to TAVR-associated afterload reduction. However, a sp...

Adequate oxygen delivery to the heart during stress is essential for sustaining cardiac function. Acute increases in myocardial oxygen demand evoke coronary vasodilation and enhance perfusion via functional upregulation of smooth muscle voltage-gated K+ (Kv) channels. Because this response is controlled by Kv1 accessory subunits (i.e., Kvβ), which...

Study objective: To garner a framework for combining community wastewater surveillance with state clinical surveillance that influence confirmation of SARS-CoV-2 variants within the community, and recommend how the flow of such research evidence could be expanded and employed for public health response. Design, setting, and participants: This work...

Rationale: Voltage-gated potassium (Kv) channels in vascular smooth muscle are essential for coupling myocardial blood flow (MBF) with the metabolic demand of the heart. These channels consist of a transmembrane pore domain that associates with auxiliary Kvβ1 and Kvβ2 proteins, which differentially regulate Kv function in excitable cells. Nonethele...

Introduction: Myocardial perfusion is enhanced during periods of elevated cardiomyocyte oxygen consumption. The coupling between blood flow and myocardial oxygen demand is mediated by redox-dependent signals, yet the influence of cardiac workload on arterial myocyte pyridine nucleotide redox status is unknown. Hypothesis: Increased cardiac workload...

Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration-suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably l...

Chronic inflammation is inextricably linked to cardiovascular disease (CVD). Macrophages themselves play important roles in atherosclerosis, as well as acute and chronic heart failure. Although the role of macrophages in CVD pathophysiology is well-recognized, little is known regarding the precise mechanisms influencing their function in these cont...

Purpose of review: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are essential regulators of gene expression. Although few lncRNAs have been the subject of detailed molecular and functional characterization, it is believed that lncRNAs play an important role in tissue homeostasis and development. In fact, gene expression profiling...

Studies in epitranscriptomics indicate that RNA is modified by a variety of enzymes. Among these RNA modifications, adenosine to inosine (A-to-I) RNA editing occurs frequently in the mammalian transcriptome. These RNA editing sites can be detected directly from RNA sequencing (RNA-seq) data by examining nucleotide changes from adenosine (A) to guan...

Abstract Induced pluripotent stem cells (iPSCs) can self-renew indefinitely in culture and differentiate into all specialized cell types including gametes. iPSCs do not exist naturally and are instead generated (“induced” or “reprogrammed”) in culture from somatic cells through ectopic co-expression of defined pluripotency factors. Since they can b...

While a majority of the mammalian genome is transcribed to RNA, mounting evidence indicates that only a minor proportion of these transcriptional products are actually translated into proteins. Since the discovery of the first non-coding RNA (ncRNA) in the 1980s, the field has gone on to recognize ncRNAs as important molecular regulators of RNA act...

While the fundamental mechanism by which cardiac cell therapy mitigates ventricular dysfunction in the post ischemic heart remains poorly defined, donor cell paracrine signaling is presumed to be a chief contributor to the afforded benefits. Of the many bioactive molecules secreted by transplanted cells, extracellular vesicles (EVs) and their prote...

Preclinical studies suggest that donor cell cardiomyogenic lineage commitment may be an important determinant of the efficacy of cardiac mesenchymal stromal cell (CMC) therapy; however, to what extent myogenic commitment influences CMC cardiac reparative capacity, as well as the underlying mechanisms by which they promote cardiac functional recover...

Preclinical investigations support the concept that donor cells more oriented towards a cardiovascular phenotype favor repair. In light of this philosophy, we previously identified HDAC1 as a mediator of cardiac mesenchymal cell (CMC) cardiomyogenic lineage commitment and paracrine signaling potency in vitro—suggesting HDAC1 as a potential therapeu...

Introduction Cardiac mesenchymal stromal cell (CMC) administration has been documented to improve cardiac function in pre‐clinical animal models of heart failure. While the precise mechanism(s) underlying their therapeutic benefits remain unclear, both transdifferentiation (contributing to formation of new cardiac parenchyma) and secretion of parac...

Ultrasound-induced microbubble destruction can enhance drug delivery to cells. The molecular weight of therapeutic compounds varies significantly (from <1kDa for small molecule drugs, to 7-15kDa for siRNAs/miRNAs, to >1000kDa for DNA plasmids). Therefore, the objective of this study was to determine the relationship between uptake efficiency and mo...

Rationale: Increasing evidence indicates the presence of long noncoding RNAs (lncRNAs) in various cell types. Airn is an imprinting gene transcribed from the paternal chromosome. It is in antisense orientation to the imprinted, but maternally-derived, Igf2r gene, on which Airn exerts its regulation in cis. Although Airn is highly expressed in the h...

Platelet count has been shown to be lower and mean platelet volume (MPV) to be higher in acute myocardial infarction (MI). However, it is not known whether these changes persist post-MI or if these measures are able to distinguish between acute thrombotic and non-thrombotic MI. Platelet count and MPV were measured in 80 subjects with acute MI (thro...

Table S1. shRNA Vectors and shRNA‐Scramble Controls Utilized in Experiments (Plasmids) Table S2. Gene‐Specific Primers With Respective Annealing Temperatures (Primers) Table S3. Antibodies With Corresponding Dilutions

Background Cardiac mesenchymal cell (CMC) administration improves cardiac function in animal models of heart failure. Although the precise mechanisms remain unclear, transdifferentiation and paracrine signaling are suggested to underlie their cardiac reparative effects. We have shown that histone deacetylase 1 (HDAC1) inhibition enhances CMC cardio...

Sonoporation of cells induced by ultrasound-driven microbubblecavitation has been utilized for intracellular delivery of molecular therapeutics. The molecular weight of therapeutic agents can vary significantly, with DNA plasmids often larger than 5 MDa, siRNAs and miRNAs ~10 kDa, and other drugs often less than 1 kDa. Some studies have suggested t...

Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac c...

Background: The authors previously reported that the c-kit-positive (c-kit(POS)) cells isolated from slowly adhering (SA) but not from rapidly adhering (RA) fractions of cardiac mesenchymal cells (CMCs) are effective in preserving left ventricular (LV) function after myocardial infarction (MI). Objectives: This study evaluated whether adherence...

Nitric oxide (NO) is a gaseous free radical molecule involved in several biological processes related to inflammation, tissue damage, and infections. Based on reports that NO inhibits migration of granulocytes and monocytes, we became interested in the role of inducible NO synthetase (iNOS) in pharmacological mobilization of hematopoietic stem/prog...

Recent Developments in Cardiovascular Research: The goal of “Recent Developments” is to provide a concise but comprehensive overview of new advances in cardiovascular research, which we hope will keep our readers abreast of recent scientific discoveries and facilitate discussion, interpretation, and integration of the findings. This will enable rea...

Background . Nitric oxide (NO) is gaseous free radical molecule involved in several biological processes related to inflammation, tissue damage, and infections. NO is synthesized by three isoforms of nitric oxide synthetase: two constitutively expressed isoforms, neuronal NOS (nNOS) and endothelial NOS (eNOS), and one isoform (iNOS) that is induced...

Background . Cell migration is a crucial process regulating the homing and mobilization of hematopoietic stem/progenitor cells (HSPCs), the trafficking of immune cells, and the metastatic spread of leukemic cells. Several factors have been described that promote cell migration, but very little is known about how this process is negatively controlle...

Histone deacetylase (HDAC) regulation is an essential process in myogenic differentiation. Inhibitors targeting the activity of specific HDAC family members have been shown to enhance the cardiogenic differentiation capacity of discrete progenitor cell types; a key property of donor cell populations contributing to their afforded benefits in cardia...

Neuron-like cells derived from adipose tissue-derived stem cells (ADSCs) have been considered as one of the most promising cells for the treatment of neurodegenerative diseases and neurotrauma in the central nervous system (CNS). Thus far, extensive efforts have been made to facilitate neuronal differentiation of ADSCs, but limited progress has bee...

1Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 2Institute of Molecular Cardiology, University of Louisville, Louisville, KY 3Institute of Meolecular Cardiology, University of Louisville, Louisville, KY Background. Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme that not only cataly...

Background . Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme that not only catalyzes the degradation of heme (e.g., released from erythrocytes) but also has an important function in various physiological and pathophysiological states associated with cellular stress, such as ischemic/reperfusion injury. HO-1 has a well-documented anti...

Alterations in chromatin structure, as mediated by the inhibition of specific HDAC family members, enhance the cardiogenic differentiation capacity of various progenitor cell types; a key property of donor cell populations shown to contribute to the benefits they provide in cardiac cell therapy applications. The influence of HDAC inhibition on card...

Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme that not only catalyzes the degradation of heme (e.g., released from erythrocytes) but also has an important function in various physiological and pathophysiological states associated with cellular stress, such as ischemic/reperfusion injury. HO-1 has a well-documented anti-inflammatory...

A recent phase I clinical trial (SCIPIO) has shown that autologous c-kit+ cardiac progenitor cells (CPCs) improve cardiac function and quality of life when transplanted into patients with ischemic heart disease. Although c-kit is widely used as a marker of resident CPCs, its role in the regulation of the cellular characteristics of CPCs remains unk...

It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vas...

There is mounting interest in using c-kit positive human cardiac stem cells (c-kitpos hCSCs) to repair infarcted myocardium in patients with ischemic cardiomyopathy. A recent phase I clinical trial (SCIPIO) has shown that intracoronary infusion of 1 million hCSCs is safe. Higher doses of CSCs may provide superior reparative ability; however, it is...

Developmental reprogramming techniques have been used to generate induced pluripotent stem (iPS) cells from both normal and malignant cells. The derivation of iPS cells from cancer has the potential to provide a unique scientific tool to overcome challenges associated with the establishment of cell lines from primary patient samples and a readily e...

Background Data are limited regarding transcatheter aortic valve replacement (TAVR)-related thrombocytopenia (TP). We sought to thoroughly characterize the presence, clinical impact, and severity of TP associated with TAVR. Methods and ResultsData were collected from 90 patients who underwent TAVR using the Edwards SAPIEN valve (59 TF, 29 TA, 2 Tao...

Prevention and reversal of left ventricular (LV) remodeling in ischemic cardiomyopathy are important therapeutic goals because LV remodeling is directly associated with adverse clinical outcomes. Although imaging parameters of remodeling are surrogate markers for clinical outcomes, the optimal surrogate end points in stem cell trials remain unknown...

Background: Cell based therapies have emerged as promising modalities in patients with ischemic cardiomyopathy, promoting reverse LV remodeling and improvement in cardiac function. It is commonly believed that the optimal methodology for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/va...

Decrements in ventricular function due to the permanent loss of contractile tissue remain problematic in patients with ischemic cardiomyopathy. For this reason, cell replacement therapy has received much popularity in recent years. Bone marrow is an abundant and accessible source of stem cells with regenerative potential. However, ischemic heart di...

Ewing sarcoma (EWS) is a highly invasive, undifferentiated tumor of unknown histogenic origin and is the second most common type of primary bone malignancy in children and young adolescents. In approximately 85% of patients, tumor development is associated with the expression of the EWS-FLI1 fusion protein generated by the t(11;22)(q24;q12) chromos...

1343 Shwachman-Diamond Syndrome (SDS) is an inherited bone marrow failure syndrome linked to defects in ribosome synthesis. The heterogeneous array of clinical findings associated with this disease state most commonly includes exocrine pancreas insufficiency, neutropenia, and metaphyseal chondroplasia. Patients also show a predisposition for progre...

Diamond-Blackfan anemia and Shwachman-Diamond syndrome are inherited bone marrow failure syndromes linked to defects in ribosome synthesis. The purpose of this study was to determine whether yeast models for Diamond-Blackfan anemia and Shwachman-Diamond syndrome differed in the mechanism by which ribosome synthesis was affected. Northern blotting,...

Nucleolar stress is a frequently invoked mechanism used to describe the pro-apoptotic phenotype of cells affected in human diseases linked to abnormalities of the ribosome. However, the diversity of clinical phenotypes observed in these diseases suggests that there may be different types of nucleolar and/or translational stress that stimulate cell...