A5072431991- Cardiomyopathy and Myosin Studies
- Viral Infections and Immunology Research
- Cardiovascular Effects of Exercise
- Muscle Physiology and Disorders
- Signaling Pathways in Disease
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Tissue Engineering and Regenerative Medicine
- Protein Kinase Regulation and GTPase Signaling
- Pluripotent Stem Cells Research
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- Integrated Circuits and Semiconductor Failure Analysis
- Pharmacological Effects and Toxicity Studies
- Metabolism, Diabetes, and Cancer
- Immune Response and Inflammation
- Burn Injury Management and Outcomes
- Respiratory Support and Mechanisms
- RNA Research and Splicing
- Electrospun Nanofibers in Biomedical Applications
- CRISPR and Genetic Engineering
- Cardiac Arrest and Resuscitation
- Cardiac Structural Anomalies and Repair
University of Michigan
2012-2023
Michigan Medicine
2022
Loyola University Chicago
1987-2014
BioWorks (United States)
2014
Feinstein Institute for Medical Research
2010
Laboratoire d’immunologie intégrative du cancer
2001-2006
National Institute of Environmental Health Sciences
2005
Cincinnati Children's Hospital Medical Center
2005
Triangle
2005
University of Illinois Chicago
1992-1996
Background— The ubiquitin proteasome system maintains a dynamic equilibrium of proteins and prevents accumulation damaged misfolded proteins, yet its role in human cardiac dysfunction is not well understood. present study evaluated function heart failure hypertrophic cardiomyopathy (HCM). Methods Results— Proteasome was studied nonfailing donor hearts, explanted failing myectomy samples from patients with HCM. proteolytic activities were markedly reduced HCM hearts compared ( P <0.01)....
Mitochondria and sarcomeres have a well-defined architectural relation that partially depends on the integrity of cytoskeletal network. An R120G missense mutation in small heat shock protein alpha-B-crystallin (CryAB) causes desmin-related cardiomyopathy. Desmin-related cardiomyopathy is characterized by formation intracellular aggregates containing CryAB desmin are amyloid positive, disease can be recapitulated transgenic mice cardiac-specific expression mutant protein.To understand...
Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that leads intensive activation the complement system. In current study, and cardiomyocyte contractility have evaluated in rats after cecal ligation puncture (CLP). Significant reductions left ventricular pressures occurred vivo vitro. These defects were prevented CLP given blocking antibody C5a. Both mRNA protein for C5a receptor (C5aR) constitutively expressed on cardiomyocytes; both...
Heterozygous mutations in sarcomere genes hypertrophic cardiomyopathy (HCM) are proposed to exert their effect through gain of function for missense or loss truncating mutations. However, allelic expression from individual has not been sufficiently characterized support this exclusive distinction human HCM.Sarcomere transcript and protein levels were analyzed septal myectomy transplant specimens 46 genotyped HCM patients with without gene 10 control hearts. For MYBPC3, the average ratio...
The functional significance of the developmental transition from slow skeletal troponin I (ssTnI) to cardiac TnI (cTnI) isoform expression in myocytes remains unclear. We show here effects adenovirus-mediated ssTnI gene transfer on myofilament structure and function adult primary culture. Gene resulted rapid, uniform, nearly complete replacement endogenous cTnI with no detected changes sarcomeric ultrastructure, or isoforms stoichiometry other proteins compared control over 7 days In studies...
Defective cardiac muscle relaxation plays a causal role in heart failure. Shown here is the new vivo application of parvalbumin, calcium-binding protein that facilitates ultrafast specialized skeletal muscles. Parvalbumin not naturally expressed heart. We show parvalbumin gene transfer to produces levels characteristic fast muscles, causes physiologically relevant acceleration performance normal hearts, and enhances an animal model slowed relaxation. may offer unique potential correct...
We studied changes in myofibrillar function and protein profiles after complete global ischemia with anoxia rat hearts. Hearts were exposed to (CGI) for 30 or 60 minutes at 37 degrees C, myofibrils prepared measurement of Ca(2+)-dependent Mg(2+)-ATPase activity pH 7.0 6.5. incubated cold saline (1 +/- 1 C) nonincubated hearts served as controls. Maximum ATPase was unchanged 6.5 from treated CGI. At 7.0, the Hill coefficient, which is an index cooperative interactions among thin-filament...
Abstract —Cardiac myosin heavy chain (MHC) isoforms are known to play a key role in defining the dynamic contractile behavior of heart during development. It remains unclear, however, whether cardiac MHC influence other important features contractility, including Ca 2+ sensitivity isometric tension To address this question, adult rats were treated chemically induce hypothyroid state and cause transition ventricular isoform expression pattern from predominantly α-MHC exclusively β-MHC...
Differentiation cultures of embryonic stem (ES) cells can be a useful in vitro system for understanding cardiac myocyte development. However, cell morphometry, sarcomere development, and functional cell-cell junction formation have not been examined detail to determine whether ES cell-derived myocytes exhibit structural characteristics similar within the developing heart. Therefore, we cellular dimensions, formation, contacts differentiating derived from mouse D3-ES cultures. Cells exhibited...
Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, proteolyzed post-MI in humans, which results an N-terminal fragment, C0-C1f. The presence of C0-C1f cultured cardiomyocytes decreased Ca(2+) transients cell shortening, abnormalities sufficient for the induction failure mouse model. However, underlying mechanisms remain unclear. Here, we investigate...
Purpose A goal of this study was to identify and investigate previously unrecognized components the remodeling process in progression heart failure by comparing protein expression ischemic failing (F) nonfailing (NF) human hearts. Experimental design Protein differences were investigated using multidimensional identification validated Western analysis. This approach detected basal lamina (BL) remodeling, further studies analyzed samples for evidence structural BL remodeling. rat model...
Abstract Mouse embryonic stem (ES) cells are totipotent derived from the inner cell mass of preimplantation blastocyst and capable differentiating in vitro into cardiac myocytes. Attached cultures ES were established to document timing contractile development by microscopic observation permit microdissection myocytes culture. The onset spontaneous contraction varied markedly differentiation culture, with being maintained on average for 9 days (range, 1 75 days). Indirect immunofluorescence...
The calcium sensitivity of tension production and the expression troponin I (TnI) T (TnT) isoforms in skinned neonatal (7 days after birth) adult rat myocardium were determined. Isometric was measured activation at a known resting sarcomere length ventricular trabeculae and, for first time, ages. Analysis tension-pCa relationships indicates greater (approximately 0.3 pCa units) compared with trabeculae. maximal isometric tension-generating ability (i.e., tension-tissue cross-sectional area)...
Familial hypertrophic cardiomyopathy (FHC) has been linked to mutations in proteins of the cardiac contractile apparatus, including α-tropomyosin (Tm). Mice expressing αTm heart were developed determine effects FHC mutant Tm on structure and function from single myocytes whole organ vivo. Expression E180G did not produce hypertrophy or detectable changes muscle morphology. However, expression increased Ca 2+ sensitivity force production a transgene expression–dependent manner. Contractile...
The heightened Ca2+ sensitivity of force found with hypertrophic cardiomyopathy (HCM)-associated mutant cardiac troponin I (cTnIR145G; R146G in rodents) has been postulated to be an underlying cause growth and premature sudden death humans animal models the disease. Expression slow skeletal TnI (ssTnI), a isoform naturally expressed developing heart, also increases myofilament sensitivity, yet its expression transgenic mouse hearts is not associated overt Gene transfer isoforms or mutants...