- Congenital heart defects research
- Heart Failure Treatment and Management
- Renin-Angiotensin System Studies
- Electrical and Bioimpedance Tomography
- Zebrafish Biomedical Research Applications
- Angiogenesis and VEGF in Cancer
- Cardiac Fibrosis and Remodeling
- Diet, Metabolism, and Disease
- Body Composition Measurement Techniques
- Trypanosoma species research and implications
- GDF15 and Related Biomarkers
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Blood Pressure and Hypertension Studies
- Cardiomyopathy and Myosin Studies
- Renal and related cancers
- Liver Disease Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Photoacoustic and Ultrasonic Imaging
- Phagocytosis and Immune Regulation
- Cardiovascular Function and Risk Factors
- Hippo pathway signaling and YAP/TAZ
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cancer, Lipids, and Metabolism
- Optical Imaging and Spectroscopy Techniques
University of California, Los Angeles
2020-2024
VA Greater Los Angeles Healthcare System
2020-2024
La Jolla Bioengineering Institute
2023
University of Buenos Aires
2002-2021
University of Southern California
2010-2019
Broad Center
2010-2016
Institute for Stem Cell Biology and Regenerative Medicine
2015
Secreted factors from the epicardium are believed to be important in directing heart ventricular cardiomyocyte proliferation and morphogenesis, although specific involved have not been identified or characterized adequately. We found that IGF2 is most prominent mitogen made by primary mouse embryonic epicardial cells a newly derived immortalized cell line called MEC1. In vivo, Igf2 expressed during midgestation development. Using whole embryo culture assay presence of inhibitors, we...
Significance A layer of fat surrounds the heart in most mammals, including humans. The biology this tissue has been speculated for centuries, but never subjected to experimental analysis because common model species are thought not have tissue. In study, we show that rodents cardiac fat, albeit a very specific location heart. We implicate origin from epicardium (the outer epithelium heart) and underlying mechanisms account its derivation. By comparing human mouse epicardial cells, provide an...
Epicardial signaling and Rxra are required for expansion of the ventricular myocardial compact zone. Here, we examine Raldh2–/– Rxra–/– mouse embryos to investigate role retinoic acid (RA) in this developmental process. The heart phenotypes Raldh2 mutants very similar characterized by a prominent defect zone growth. Although RA activity is completely lost epicardium adjacent myocardium, not hearts, suggesting that epicardium/myocardium formation. We explored possibility RA-mediated target...
Complementary to mainstream cardiac imaging modalities for preclinical research, photoacoustic computed tomography (PACT) can provide functional optical contrast with high speed and resolution. However, PACT has not been demonstrated reveal the dynamics of whole anatomy or vascular system without surgical procedure (thoracotomy) tissue penetration. Here, we achieved non-invasive rat hearts using recently developed three-dimensional (3D-PACT) platform, demonstrating regulated illumination...
Exercise promotes pulsatile shear stress in the arterial circulation and ameliorates cardiometabolic diseases. However, exercise-mediated metabolic transducers for vascular protection remain under-investigated. Untargeted metabolomic analysis demonstrated that wild-type mice undergoing voluntary wheel running exercise expressed increased endothelial stearoyl-CoA desaturase 1 (SCD1) catalyzes anti-inflammatory lipid metabolites, namely, oleic (OA) palmitoleic acids (PA), to mitigate...
The strategies that control formation of the ventricular wall during heart development are not well understood. In previous studies, we documented IGF2 as a major mitogenic signal controls cardiomyocyte proliferation and chamber expansion. Our objective in this study was to define tissue source upstream pathways its expression. Using number mouse genetic tools, confirm critical is epicardium. We find epicardial Igf2 expression controlled biphasic manner, first induced by erythropoietin then...
Rationale: Macrophages are the frontline immune cells in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Angiotensin-converting enzyme (ACE2) serves as binding receptor SARS-CoV-2 Spike glycoprotein for fusion and internalization into human host cells.However, mechanisms underlying SARS-CoV-2-elicited macrophage inflammatory responses remain elusive.Neutralizing by ACE2 (hACE2) decoys has been proposed a therapeutic approach ameliorate SARS-CoV-2-stimulated...
The embryonic day E10-13 period of mouse heart development is characterized by robust cardiomyocyte proliferation that creates the compact zone thickened ventricular wall myocardium. This process initiated formation epicardium on outer surface, which releases insulin-like growth factor 2 (IGF2) as primary mitogen. Two receptors mediate IGF2 signaling, IGF1R and insulin receptor (INSR).In this study, we addressed relative roles two in development. We find both are expressed during period,...
To characterize the temporal activation of renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT(1)R) expression and levels from 3 h to 35 days. The effects losartan (12.5 mg.kg(-1).day(-1)) on functional histomorphometric parameters when treatment was initiated early (3 h) late (day 15) post-MI maintained for different periods time [short term (4 days), midterm (20 long (35 days)] were also studied. AT(1)R increased MI zone at...
Wall shear stress (WSS) contributes to the mechanotransduction underlying microvascular development and regeneration. Using computational fluid dynamics, we elucidated interplay between WSS vascular remodelling in a zebrafish model of tail amputation The transgenic
To investigate cardiomyocyte hypertrophy and hormonal profile in cardiac resulting from sequentially applied overloads.We studied Sprague-Dawley rats with renovascular hypertension (RV), where pressure overload predominates, or deoxycorticosterone acetate (DOCA)-salt (DS), volume at 2 4 weeks of treatment, the combination both models inverse sequence: RV weeks/DS (RV2/DS2) DS weeks/RV (DS2/RV2), their sham controls (Sh).Blood diameter increased to a similar extent combined models....
<i>Background:</i> The present study was performed to explore the effect of exogenous infusions atrial natriuretic peptide (ANP) on early inflammatory response during acute sodium overload in normal rats. <i>Methods:</i> Sprague Dawley rats were exposed (Na 1.5 <i>M</i>). Nonhypotensive doses ANP (1 and 5 µg ·kg<sup>–1</sup> ·h<sup>–1</sup>) infused simultaneously with or after infusion order evaluate prevention reversion response,...
Hemodynamic parameters and natriuretic peptide levels were evaluated in cardiac hypertrophy produced by sequentially applied renovascular (RV) deoxycorticosterone acetate-salt (DS) models of hypertension. We studied hypertensive rats RV or DS treatment at 2 4 wk, as well the combination wk each an inverse sequence: wk/DS (RV2/DS2) wk/RV (DS2/RV2). The vivo function, interstitial fibrosis, synthesis secretion types A (ANP) B (BNP) peptides monitored compared with their corresponding sham...
Summary 1 A fructose (Fru)‐enriched diet induces a mild increase in blood pressure associated with hyperglycaemia, hypertriglyceridaemia, and insulin resistance, resembling the human ‘syndrome X’, being an useful model to study hypertension type 2 diabetes. sustained elevation of is cardiovascular structural modifications such as left ventricular hypertrophy increased wall thickness:lumen diameter ratio vessels. 3 Prostanoids (PR), metabolites arachidonic acid through cyclooxygenase pathway,...
The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats pressure (renovascular) or volume overload (DOCA-salt) 6 and 12 weeks treatment. also consecutive combination both models inverse sequences: RV weeks/DS DS weeks/RV weeks. All treated groups developed hypertension. Cardiac hypertrophy left ventricular ANP gene expression were more pronounced single...
Electrical impedance spectroscopy (EIS) has been recognized to characterize oxidized low-density lipoprotein (oxLDL) in the metabolically active plaque. However, intravascular deployment of 3-D EIS-derived electrical tomography (EIT) for endoluminal mapping oxLDL-laden arterial walls remains an unmet clinical challenge. To this end, we designed 6-point microelectrode arrays that were circumferentially configurated onto balloon catheter 15 EIS permutations. In parallel, created plaques by...
Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes cardiometabolic diseases in overweight individuals. While biopsy current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) a non-invasive alternative still under clinical trials, former invasive latter costly. We demonstrate electrical impedance tomography (EIT) as portable method for detecting infiltrate. enrolled 19 subjects undergo MRI scans, followed by EIT measurements. The images...
A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations rats. Our hypothesis was that protein kinase C (PKC) activation, reported the acute period of fructose overload, and impaired vessel's response to vasoactive substances contribute maintain elevated levels chronic period. The aims this study were investigate animal model hypertension: (1) if PKC activation also found stage; (2) involvement nitric oxide insulin response; plasma atrial...
Abstract Within vascular networks, wall shear stress (WSS) modulates endothelial cell proliferation and arteriovenous specification. Mechano-responsive signaling pathways enable vessels within a connected network to structurally adapt properly partition blood flow between different parts of organ systems. Here, we study regeneration in zebrafish model system, performing tail amputation the Dorsal Aorta (DA)-Posterior Cardinal Vein (PCV) embryonic circulatory loop (ECL) at 3 days post...