A5003393607- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Cancer Mechanisms and Therapy
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Mitochondrial Function and Pathology
- Electrospun Nanofibers in Biomedical Applications
- Cardiovascular Effects of Exercise
- Cardiac Structural Anomalies and Repair
- RNA modifications and cancer
- Receptor Mechanisms and Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cardiac Ischemia and Reperfusion
- Mechanisms of cancer metastasis
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Muscle Physiology and Disorders
- Autophagy in Disease and Therapy
- Smoking Behavior and Cessation
San Diego State University
2015-2024
Jabil (United States)
2018-2024
Regenerative Medicine Institute
2016-2024
GTx (United States)
2019
California Institute for Regenerative Medicine
2014-2018
American College of Cardiology
2018
BG University Hospital Bergmannsheil Bochum
2018
Palo Alto Institute
2018
Hospital General Universitario Gregorio Marañón
2018
Centro de Investigación Biomédica en Red
2018
To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of senescence, cell death, telomerase activity, telomere integrity, regeneration were measured in myocytes wild-type mice (WT). These parameters similarly studied insulin-like growth factor-1 (IGF-1) transgenic (TG) because IGF-1 promotes survival may delay aging. Importantly, the consequences on cardiac stem (CSC) senescence evaluated. Gene products implicated arrest such as p27 Kip1 , p53, p16 INK4a...
Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it shown calcineurin, a calcium-regulated phosphatase, plays critical role the pathogenesis HCM. Administration calcineurin inhibitors cyclosporin and FK506 prevented mice were genetically predisposed to develop HCM as result aberrant expression tropomodulin, myosin light chain–2, or fetal β-tropomyosin heart. Cyclosporin had similar effect rat model pressure-overload hypertrophy....
Background— Because mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit + cardiac (CSCs) in vivo vitro, we hypothesized that combining human (h) MSCs with hCSCs produces greater infarct size reduction compared either cell administered alone after myocardial infarction (MI). Methods Results— Yorkshire swine underwent balloon occlusion the left anterior descending coronary artery followed by reperfusion were immunosuppressed MI cyclosporine methylprednisolone....
The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, notion BMC transdifferentiation questioned. center controversy is lack unequivocal evidence in favor myocardial regeneration by injection BMCs infarcted heart. Because interest cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based...
Cell-based therapies represent a very promising strategy to repair and regenerate the injured heart prevent progression failure. To date, these have had limited success due lack of survival retention infused cells. Therefore, it is important increase our understanding biology cells utilize this information enhance their function in heart. Mitochondria are critical for progenitor cell survival. Here, we demonstrate importance mitochondrial autophagy, or mitophagy, differentiation process...
Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic BCL-2 protein that up-regulated in several human cancers. MCL-1 also highly expressed myocardium, but its function myocytes has not been investigated. We generated inducible, cardiomyocyte-specific Mcl-1 knockout mice and found ablation of the adult heart led to rapid cardiomyopathy death. Although known inhibit apoptosis, this process was activated MCL-1-deficient hearts. Ultrastructural analysis revealed disorganized sarcomeres swollen...
Ischemia/reperfusion (I/R) affects the integrity of endoplasmic reticulum (ER), site synthesis and folding numerous proteins. Therefore, I/R may activate unfolded protein response (UPR), resulting in induction a collection ER stress proteins, many which are protective function to resolve stress. In this study, we showed that when mouse hearts were subjected ex vivo I/R, levels 2 stress-inducible markers UPR, ER-targeted cytoprotective chaperones glucose-regulated proteins 78 94 (GRP78...
Endoplasmic reticulum (ER) stresses that reduce ER protein folding activate the unfolded response (UPR). One effector of UPR is transcription factor X-box binding protein-1 (XBP1), which expressed on stress-mediated splicing XBP1 mRNA. induces certain ER-targeted proteins, eg, glucose-regulated 78 (GRP78), help resolve stress and foster cell survival. In this study, we determined whether hypoxia can in cardiac context. Neonatal rat ventricular myocyte cultures subjected to (16 hours)...
Cardiovascular disease risk is higher in men than women, but the basis for this discrepancy remains controversial. Estrogenic stimulation of myocardium or isolated cardiomyocytes has been purported to exert multiple beneficial effects associated with inhibition maladaptive responses pathogenic insults. This report describes a significant difference between sexes myocardial activation Akt, protein kinase that regulates broad range physiological including metabolism, gene transcription, and...
Background —Failing human hearts are characterized by altered cytoskeletal and myofibrillar organization, impaired signal transduction, abnormal protein turnover, energy metabolism. Thus, expression of multiple classes genes is likely to be in heart failure. Methods Results —We used high-density oligonucleotide arrays explore changes ≈7000 2 nonfailing failing with diagnoses end-stage ischemic dilated cardiomyopathy, respectively. We report (1) (striated muscle LIM protein-1 [SLIM1],...
Heart failure is associated with death of cardiomyocytes leading to loss contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition cell and prevention pathogenesis induced by cardiomyopathic stimuli. However, recent our group have found accumulation activated the nucleus, suggesting that biologically relevant target(s) activity may be located there. To test this hypothesis, a targeted construct was created...
Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing regenerative potential adoptively transferred cardiac progenitor (CPCs) via genetic engineering overexpress Pim-1, a cardioprotective kinase that enhances cell survival proliferation.Intramyocardial injections CPCs...
Background— The anthracycline doxorubicin is an effective chemotherapeutic agent used to treat pediatric cancers but associated with cardiotoxicity that can manifest many years after the initial exposure. To date, very little known about mechanism of this late-onset cardiotoxicity. Methods and Results— understand problem, we developed a model doxorubicin-induced in which juvenile mice were exposed doxorubicin, using cumulative dose did not induce acute These normally had no obvious cardiac...
The Notch network regulates multiple cellular processes, including cell fate determination, development, differentiation, proliferation, apoptosis, and regeneration. These processes are regulated via Notch-mediated activity that involves hepatocyte growth factor (HGF)/c-Met receptor phosphatidylinositol 3-kinase/Akt signaling cascades. impact of HGF on was assessed following myocardial infarction as well in cultured cardiomyocytes. Notch1 is activated border zone cardiomyocytes coincident...
The endoplasmic reticulum (ER) stress response (ERSR) is activated when folding of nascent proteins in the ER lumen impeded. Myocardial ischemia was recently shown to activate ERSR; however, role this complex signaling system heart not well understood. activates transcription factor ATF6, which induces expression targeted ER, where they restore protein folding, thus fostering cytoprotection. We previously developed a transgenic mouse line that expresses conditionally form ATF6 heart. In...
Pulmonary artery hypertension (PAH) is a proliferative disorder associated with enhanced pulmonary smooth muscle cell proliferation and suppressed apoptosis. The sustainability of this phenotype required the activation prosurvival transcription factor like signal transducers activators transcription-3 (STAT3) nuclear activated T (NFAT). Because these factors are implicated in several physiological processes, their inhibition PAH patients could be detrimental effects. Therefore, better...