A5013532679- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Elasticity and Material Modeling
- Cardiac Structural Anomalies and Repair
- Cardiac Fibrosis and Remodeling
- Cellular Mechanics and Interactions
- Cardiac pacing and defibrillation studies
- Cardiovascular Effects of Exercise
- Congenital Heart Disease Studies
- Cardiac Arrhythmias and Treatments
- Cardiac Valve Diseases and Treatments
- Tissue Engineering and Regenerative Medicine
- Advanced MRI Techniques and Applications
- Signaling Pathways in Disease
- Electrospun Nanofibers in Biomedical Applications
- Congenital heart defects research
- Advanced Neuroimaging Techniques and Applications
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Orthopaedic implants and arthroplasty
- Neuroscience and Neural Engineering
- Cardiac Imaging and Diagnostics
- Connective tissue disorders research
- Acute Myocardial Infarction Research
University of California, San Diego
2015-2024
La Jolla Bioengineering Institute
2008-2023
Simula Research Laboratory
2014
University of California, Davis
2014
Bioengineering Center
2006-2013
UC San Diego Health System
2012
Jeffrey Modell Foundation
2011
Medtronic (United States)
2010
Medtronic (Ireland)
2010
National Institutes of Health
2006
The response of cardiomyocytes to biomechanical stress can determine the pathophysiology hypertrophic cardiac disease, and targeting pathways regulating these responses is a therapeutic goal. However, little known about how sensed by cardiomyocyte sarcomere transduce intracellular signals or dysfunction may lead disease. Here, we found that four-and-a-half LIM domains 1 (FHL1) part complex within senses stress–induced important for hypertrophy. Mice lacking Fhl1 displayed blunted beneficial...
Residual stress in an organ is defined as the that remains when all external loads are removed. has generally been ignored published papers on left ventricular wall stress. To take residual into account analysis of distributions a beating heart, one must first measure strain no-load state heart. strains equatorial cross-sectional rings (2-3 mm thick) five potassium-arrested rat ventricles were measured. The effects friction and loading reduced by submersing specimen fluid, hypothermic,...
Sphingosine 1-phosphate (S1P) is released at sites of tissue injury and effects cellular responses through activation G protein-coupled receptors. The role S1P in regulating cardiomyocyte survival following vivo myocardial ischemia-reperfusion (I/R) was examined by using mice which specific receptor subtypes were deleted. Mice lacking either 2 or 3 receptors subjected to 1-h coronary occlusion followed h reperfusion developed infarcts equivalent those wild-type (WT) mice. However, 2,3...
Actin-myosin interactions provide the driving force underlying each heartbeat. The current view is that actin-bound regulatory proteins play a dominant role in activation of calcium-dependent cardiac muscle contraction. In contrast, relevance and nature regulation by myosin (for example, light chain-2 [MLC2]) remain poorly understood. By integrating gene-targeted mouse computational models, we have identified an indispensable for ventricular Mlc2 (Mlc2v) phosphorylation regulating Cardiac...
Post-surgical cardiac adhesions represent a significant problem during routine cardiothoracic procedures. This fibrous tissue can impair heart function and inhibit surgical access in reoperation Here, we propose hydrogel barrier composed of oxime crosslinked poly(ethylene glycol) (PEG) with the inclusion catechol (Cat) group to improve retention on for pericardial adhesion prevention. three component system is comprised aldehyde (Ald), aminooxy (AO), Cat functionalized PEG mixed form final...
Abstract Because cell shape and alignment, cell–matrix adhesion, cell–cell contact can all affect growth, because mechanical strains in vivo are multiaxial anisotropic, we developed an vitro system for engineering aligned, rod‐shaped, neonatal cardiac myocyte cultures. Photolithographic microfluidic techniques were used to micropattern extracellular matrices parallel lines on deformable silicone elastomers. Confluent, elongated, aligned myocytes produced by varying the line width collagen...
Early relaxation in the cardiac cycle is characterized by rapid torsional recoil of left ventricular (LV) wall. To elucidate contribution transmural arrangement myofiber to relaxation, we determined time course three-dimensional fiber-sheet strains anterior wall five adult mongrel dogs vivo during early with biplane cineangiography (125 Hz) implanted markers. Fiber-sheet were found from fiber and sheet orientations directly measured heart tissue. The strain was epicardial, midwall,...
Quantitative assessment of myofiber disarray associated with diseases such as familial hypertrophic cardiomyopathy (FHC) can be performed by estimating local angular deviation fiber orientation in histologic sections. The large number measurements required to estimate prohibits manual measurement. We describe methods for automated measurement and tissue sections from transgenic mice ventricular expression ras, proposed a model FHC. Images normal were analyzed using image processing...
Abstract —Because the amount and structure of type I collagen are thought to affect mechanics ventricular myocardium, we investigated myocardial passive mechanical function in osteogenesis imperfecta murine ( oim ) model pro-α2(I) deficiency, previously shown have less impaired biomechanics tendon bone. Compared with wild-type littermates, homozygous hearts exhibited 35% lower area fraction P <0.05), 38% fiber number density 42% smaller diameter <0.05). wild-type, left (LV)...
Brief ischemic periods lead to myocardial dysfunction without infarction. It has been shown that expression of inducible HSP70 in hearts transgenic mice leads decreased infarct size, but it remains unclear if can also protect against after brief ischemia. To investigate this question, we developed a mouse model which regional function be measured before and temporary event vivo. In addition, was determined episodes global ischemia an isolated Langendorff heart. HSP70-positive transgene...
Background— Myocardial infarction (MI) is associated with early metalloproteinase (MMP) activation and extracellular matrix (ECM) degradation. We hypothesized that preserving the original ECM of infarcted left ventricle (LV) by use short-term doxycycline (DOX) treatment preserves cardiac structure function. Methods Results— LV morphometry function were measured in 3 groups rats (sham, MI, MI+DOX). DOX (30 mg/kg per day) was given orally 48 hours before after MI. Rats examined at 2 4 weeks By...
Three-dimensional myocardial strains in seven isolated, potassium-arrested dog hearts were measured by biplane radiography of 3 transmural columns 4-6 radiopaque beads implanted the midanterior left ventricular free wall. Transmural distributions strain during inflation a balloon to 20-30 mmHg computed with respect zero pressure state. Magnitudes principal increased proportion volume (0.0088, 0.0037, and -0.0059 ml-1). At 8 +/- 4 mmHg, mean circumferential (E11) longitudinal (E22) similar,...
Several injectable materials have been shown to preserve or improve cardiac function as well prevent slow left ventricular (LV) remodeling post-myocardial infarction (MI). However, it is unclear whether the structural support bioactivity of these polymers that lead beneficial effects. Herein, we examine how passive enhancement LV wall by an increase in thickness affects post-MI using a bio-inert, non-degradable synthetic polymer effort better understand mechanisms which affect...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) termed a 'disease of the desmosome' is an inherited that recently underwent reclassification owing to identification left-dominant and biventricular disease forms. Homozygous loss-of-function mutations in desmosomal component, desmoplakin, are found patients exhibiting form ARVC; however, no models recapitulate postnatal hallmarks as seen these patients. To gain insights into homozygous effects desmoplakin heart, we generated...
The maturation of cardiac myocytes during the immediate prenatal period coincides with changes in mechanical properties extracellular matrix. We investigated effects stiffness on cardiomyocyte neonatal rat ventricular grown collagen‐coated gels. Cells 10‐kPa substrates developed aligned sarcomeres, while cells stiffer had unaligned sarcomeres and stress fibers. generated greater force gels similar to that native myocardium than or softer substrates. To investigate differentiation myocyte...