A5040043727- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- Signaling Pathways in Disease
- Histone Deacetylase Inhibitors Research
- Cardiovascular Function and Risk Factors
- Peptidase Inhibition and Analysis
- Pluripotent Stem Cells Research
- Electrospun Nanofibers in Biomedical Applications
- Cardiac Fibrosis and Remodeling
- Cardiovascular Effects of Exercise
- Congenital heart defects research
- Heart Failure Treatment and Management
- Cardiac Structural Anomalies and Repair
- Muscle Physiology and Disorders
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- 3D Printing in Biomedical Research
- Estrogen and related hormone effects
- RNA Research and Splicing
- Ion channel regulation and function
- Sarcoidosis and Beryllium Toxicity Research
- Diabetes Treatment and Management
- NF-κB Signaling Pathways
- Sex and Gender in Healthcare
- Peripheral Artery Disease Management
Exempla Saint Joseph Hospital
2023
Colorado Permanente Medical Group
2023
University of Colorado Anschutz Medical Campus
2007-2021
Kaiser Permanente
2020
University of Colorado Denver
2005-2019
MARK Resources (United States)
2015-2019
University of Colorado Boulder
2017
University of Trieste
2016
International Centre for Genetic Engineering and Biotechnology
2016
Denver Health Medical Center
2005-2013
Direct reprogramming of fibroblasts into cardiomyocytes by forced expression cardiomyogenic factors, GMT (GATA4, Mef2C, Tbx5) or GHMT Hand2, Tbx5), has recently been demonstrated, suggesting a novel therapeutic strategy for cardiac repair. However, current approaches are inefficient. Here we demonstrate that pro-fibrotic signalling potently antagonizes reprogramming. Remarkably, inhibition using small molecules target the transforming growth factor-β Rho-associated kinase pathways converts...
The histone deacetylase inhibitor ITF2357 (givinostat) prevents diastolic dysfunction by enhancing cardiac myofibril relaxation.
Little is known about the function of cytoplasmic histone deacetylase HDAC6 in striated muscle. Here, we addressed role cardiac and skeletal muscle remodeling induced by peptide hormone angiotensin II (ANG II), which plays a central blood pressure control, heart failure, associated wasting. Comparable with wild-type (WT) mice, null mice developed hypertrophy fibrosis response to ANG II. However, whereas WT systolic dysfunction upon treatment II, was maintained treated for up 8 wk. The...
Cardiac hypertrophy is a strong predictor of morbidity and mortality in patients with heart failure. Small molecule histone deacetylase (HDAC) inhibitors have been shown to suppress cardiac through mechanisms that remain poorly understood. We report class I HDACs function as signal-dependent repressors via inhibition the gene encoding dual-specificity phosphatase 5 (DUSP5) DUSP5, nuclear negatively regulates prohypertrophic signaling by ERK1/2. Inhibition DUSP5 requires activity ERK kinase,...
Mutations in lysosomal-associated membrane protein 2 (LAMP-2) gene are associated with Danon disease, which often leads to cardiomyopathy/heart failure through poorly defined mechanisms. Here, we identify the LAMP-2 isoform B (LAMP-2B) as required for autophagosome-lysosome fusion human cardiomyocytes (CMs). Remarkably, LAMP-2B functions independently of syntaxin 17 (STX17), a that is essential non-CMs. Instead, interacts autophagy related 14 (ATG14) and vesicle-associated 8 (VAMP8) its...
Histone deacetylase inhibition counteracts adverse left ventricular remodeling, improves pulmonary function, and reverses diastolic dysfunction.
Tension production and contractile properties are poorly characterized aspects of excitation-contraction coupling human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Previous approaches have been limited due to the small size structural immaturity early-stage hiPSC-CMs. We developed a substrate nanopatterning approach produce hiPSC-CMs in culture with adult-like dimensions, T-tubule-like structures, aligned myofibrils. then isolated myofibrils from measured tension...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they immature, which is barrier to modeling adult-onset cardiovascular disease. Here, we sought develop simple method that could drive cultured hiPSC-CMs toward maturity across number of phenotypes, with the aim utilizing mature model human were in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics adult...
Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening associated with development diastolic dysfunction (DD), while augmented titin compliance appears to impair systolic performance in dilated cardiomyopathy. We found that myofibril was elevated mice lacking histone deacetylase 6 (HDAC6). Cultured adult murine ventricular myocytes treated selective HDAC6 inhibitor also exhibited...
The ability of the adult heart to regenerate cardiomyocytes (CMs) lost after injury is limited, generating interest in developing efficient cell-based transplantation therapies. Rigid carbon nanotubes (CNTs) scaffolds have been used improve CMs viability, proliferation, and maturation, but they require undesirable invasive surgeries for implantation. To overcome this limitation, we developed an injectable reverse thermal gel (RTG) functionalized with CNTs (RTG-CNT) that transitions from a...
Alterations in TR [thyroid hormone (TH) receptor]1 isoform expression have been reported models of both physiologic and pathologic cardiac hypertrophy as well patients with heart failure. In this report, we demonstrate that TH induces a direct result binding to the TRalpha1 and, moreover, overexpression alone is also associated hypertrophic phenotype, even absence ligand. The mechanism TRalpha1-specific novel for nuclear receptor involves transforming growth factor beta-activated kinase...
Although cardiovascular disease is the primary killer of women in United States, and female animals have traditionally been omitted from research studies. In reports that do include both sexes, significant sexual dimorphisms demonstrated development, presentation, outcome disease. However, there little understanding mechanisms underlying these observations. A more thorough sex-specific differences at baseline required to effectively consider treat all patients with disease.We analyzed...
Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies growing, but sustainability of injected CMs remains challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided solution-based delivery vehicle CMs, which transitioned gel-based matrix shortly after reaching body temperature. In this...
Myofibril based mechanical studies allow evaluation of sarcomeric protein function. We describe a novel method obtaining myofibrils from primary cardiomyocyte culture. Adult rat ventricular myocytes (ARVMs) were obtained by enzymatic digestion and maintained in serum free condition. ARVMs homogenized relaxing solution (pCa 9.0) with 20% sucrose, myofibril suspension was made. Myofibrils Ca2+-activated relaxed at 15°C. Results ARVM compared to tissue skinned Triton X-100. At maximal...
Background— Although induction of activator protein-1 (AP-1) transcription factor activity has been observed in cardiac hypertrophy, a direct role for AP-1 myocardial growth and gene expression remains obscure. Methods Results— Hypertrophy was induced cultured neonatal rat cardiomyocytes with phenylephrine or overexpression constitutively active MAP3K, MKK6. In both treatment groups, the pathological profile observed, ie, β-myosin heavy chain (βMHC), atrial/brain natriuretic peptides...
Using neonatal rat ventricular myocytes, we previously reported that the expression of a dominant negative form c-Fos proto-oncogene (AFos) inhibited activator protein 1 activity and blocked induction pathological gene profile stimulated by phenylephrine (PE) while leaving growth unaffected. We now extend these observations to adult myocyte (ARVM) understand relationship between expression, growth, function. Ventricular myocytes were isolated from rats infected with adenovirus expressing...
Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, infiltrative form of heart failure (HF). Nevertheless, ATTR-CM largely underrecognized and misdiagnosed condition. This study's objective was to develop an efficient model assess the chance in patients with HF. Methods observational study HF who had confirmed diagnosis those but without known between January 1, 2019, July 2021. Patient characteristics were extracted from administrative claims electronic databases...
A 60-year-old man with a history of Child-Pugh class B cirrhosis was admitted to the hospital 4-5 days nausea, vomiting and altered mental status. Following development fever in intensive care unit methicillin-sensitive Staphylococcus aureus bacteraemia, large (15 mm) vegetation discovered on anterolateral papillary muscle mitral valve. thorough multidisciplinary evaluation, patient considered be poor surgical candidate due significant perioperative complications associated cirrhosis. The...