A5071988592- Renin-Angiotensin System Studies
- Hormonal Regulation and Hypertension
- Renal Diseases and Glomerulopathies
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Extracellular vesicles in disease
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Adipose Tissue and Metabolism
- Chronic Kidney Disease and Diabetes
- Hearing, Cochlea, Tinnitus, Genetics
- Receptor Mechanisms and Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular Function and Risk Factors
- Cancer-related molecular mechanisms research
- Alzheimer's disease research and treatments
- Phagocytosis and Immune Regulation
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Growth Hormone and Insulin-like Growth Factors
- Cellular Mechanics and Interactions
- Renal and Vascular Pathologies
- Fibroblast Growth Factor Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Marine animal studies overview
- Pulmonary Hypertension Research and Treatments
Mayo Clinic in Arizona
2017-2025
Mayo Clinic
2018-2023
WinnMed
2018-2023
University of Missouri
2006-2008
Harry S. Truman Memorial Veterans' Hospital
2006-2008
Wake Forest University
2008
Banner - University Medical Center Tucson
2007
University of Arizona
2006
Imaging Center
2006
TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, manifest hypertension, and exhibit increased tissue ANG II levels oxidative stress. Evidence indicates that elevated contributes to stress, increases in glomerular macromolecular permeability, consequent albuminuria. Furthermore, angiotensin type 1 receptor (AT1R) blockers reduce albuminuria slow progression of renal disease. However, it is not known whether improvements filtration barrier integrity during treatment are...
Diet-induced insulin resistance (IR) adversely affects human health and life span. We show that muscle-specific overexpression of mitochondrial transcription factor A (TFAM) attenuates high-fat diet (HFD)-induced fat gain IR in mice conjunction with increased energy expenditure reduced oxidative stress. These TFAM effects on muscle are shown to be exerted by molecular changes beyond its direct effect DNA replication transcription. augmented the tricarboxylic acid cycle citrate synthase...
The renin-angiotensin-aldosterone system contributes to cardiac remodeling, hypertrophy, and left ventricular dysfunction. Angiotensin II aldosterone (corticosterone in rodents) together generate reactive oxygen species (ROS) via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which likely facilitate this hypertrophy remodeling. This investigation sought determine whether oxidative stress cellular remodeling could be attenuated by vivo mineralocorticoid receptor (MR)...
Activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase by angiotensin II is integral to the formation oxidative stress in vasculature and kidney. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibition associated with reductions kidney decreases albuminuria. Effects 3-hydroxy-3-methylglutaryl-coenzyme on filtration barrier integrity are poorly understood. To investigate, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor mouse renin transgene...
Angiotensin II (ANG II) contributes to cardiac remodeling, hypertrophy, and left ventricular dysfunction. ANG stimulation of the type 1 receptor (AT(1)R) generates reactive oxygen species via NADPH oxidase, which facilitates this hypertrophy remodeling. This investigation sought determine whether oxidative stress cellular remodeling could be attenuated by in vivo AT(1)R blockade (AT(1)B) (valsartan) or superoxide dismutase/catalase mimetic (tempol) treatment a rodent model chronically...
The transgenic (mRen2)27 (Ren2) rat overexpresses mouse renin in extrarenal tissues, causing increased local synthesis of ANG II, oxidative stress, and hypertension. However, little is known about the role stress induced by tissue renin-angiotensin system (RAS) as a contributing factor pulmonary hypertension (PH). Using male Ren2 rats, we test hypothesis that lung RAS overexpression resultant contribute to PH vascular remodeling. Mean arterial pressure (MAP), right ventricular systolic...
The fibrogenic wound-healing response in liver increases stiffness. Here, macro and microheterogeneity of stiffness correlate with HSC heterogeneity a hepatic fibrosis mouse model. Fibrogenic HSCs localized stiff collagen-high areas upregulate the expression focal adhesion molecule FHL2, which, turn, promotes extracellular matrix protein expression. These results demonstrate that at whole organ, lobular, cellular level drives an amplification loop fibrogenesis through specific molecular pathways.
Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), release fibrogenic nanosized extracellular vesicles (EVs), and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated up-regulation EV-related pericentral zone,...
Angiotensin-II (Ang-II)-stimulated increases in nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity and oxidative stress are known to play a key role cardiac remodeling. Inhibition of isoprenylation activation small G proteins, such as Rac1, component NADPH oxidase, may mediate the antioxidant actions 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). In this study, we investigated effects rosuvastatin on remodeling transgenic rats (Ren2)...
Angiotensin II (Ang II) stimulation of the Ang type 1 receptor (AT R) facilitates myocardial remodeling through NADPH oxidase-mediated generation oxidative stress. Components renin-angiotensin system constitute an autocrine/paracrine unit in myocardium, including renin, which is rate-limiting step II. This investigation sought to determine whether cardiac stress and cellular could be attenuated by vivo renin inhibition and/or AT R blockade a rodent model chronically elevated tissue levels,...
<i>Background/Aim:</i> There is an emerging relationship between insulin resistance/hyperinsulinemia, oxidative stress, and glomerular injury manifesting as albuminuria. HMG-CoA reductase inhibitors (statins) have been shown to reduce stress in the vasculature well albuminuria animal models human studies. The filtration barrier a critical determinant of albumin filtration. We investigated effects resistance rosuvastatin or placebo on barrier. <i>Method:</i> Young...
Abstract Immunoglobulin light chain (AL) amyloidosis is a fatal complication of B‐cell proliferation secondary to deposition amyloid fibrils in various organs. Urinary exosomes (UEX) are the smallest microvesicles excreted urine. Previously, we found UEX patients with AL contained immunoglobulin (LC) oligomers that multiple myeloma did not have. To further explore role LC oligomers, was isolated from an patient progressive renal disease despite achieving complete response. were identified....
TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for reabsorption of 5-8 g glomerular filtered albumin each day. Excess may contribute to PTC damage tubulointerstitial disease. This investigation examined role II-induced oxidative stress in structural remodeling: whether such changes could be modified vivo treatment type 1 receptor (AT(1)R) blockade...
To investigate whether controlled early loading enhances peri-implant bone mass and bone-to-implant contact. Low-frequency stimulation (3 Hz) varying force amplitudes, causing strains, were applied in three guinea-pig series.Three series of guinea-pigs received percutaneous TiO(2)-blasted implants both tibiae. One week after implant installation, one was stimulated with a sinusoidally bending moment while the contra-lateral served as an unloaded control. Force amplitudes 0.5, 1 2 N on...
Myocardium is flexible when it comes to energy substrate utilization; uses fatty acid, glucose, lactones, and ketones for its requirement. The myocardial preference varies in a dynamic manner depending on perfusion, demand, availability, local/systemic hormonal changes. authors discuss the metabolic perturbations seen insulin-resistant myocardium how they result structural other biochemical changes that ultimately left ventricular hypertrophy diastolic systolic dysfunction. also utility of...
Our understanding of inner ear hair cell ultrastructure has heretofore relied upon two-dimensional imaging; however, serial block-face scanning electron microscopy (SBFSEM) changes this paradigm allowing for three-dimensional evaluation. We compared cells the apical cristae in myo7aa−/− null zebrafish, a model human Usher Syndrome type 1B, to wild-type zebrafish by SBFSEM investigate possible ribbon synapse ultrastructural differences. Previously, it been shown that wild type, neuromast have...
Light Chain (AL) Amyloidosis is a plasma cell dyscrasia producing amyloidogenic light chains (LC) that misfold and form amyloid deposits cause damage in vital organs, primarily the heart kidneys. Urinary extracellular vesicles (uEVs) are nanoparticles produced by renal epithelial cells throughout nephron. We previously showed uEVs from active AL amyloidosis patients contain LC oligomers large (>250kDa), resistant to heat chemical denaturation, but of low abundance. Renal dysfunction results...