Circulatory and Respiratory Physiology Commons^™

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Ray Daniels

Electronic Theses and Dissertations

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Mobilizing Mechanically Ventilated Neuroscience Patients - A Clinical Practice Guideline To ‘Get Up And Go’, Bonnie Wasilowsky Bspa-Hca, Rn, Cnrn

Patient Care Services / Nursing

No abstract provided.

Growth Of Nasal And Laryngeal Airways In Children: Implications In Breathing And Inhaled Aerosol Dynamics, Jinxiang Xi, Xiuhua Si, Yue Zhou, Jong Won Kim

University Faculty Publications and Creative Works

BACKGROUND: The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old …

Growth Of Nasal And Laryngeal Airways In Children: Implications In Breathing And Inhaled Aerosol Dynamics, Jinxiang Xi, Xiuhua Si, Yue Zhou, Jong Won Kim

University Faculty Publications and Creative Works

The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old adult. …

The Role Of Bioactive Lipids In Stem Cell Mobilization And Homing: Novel Therapeutics For Myocardial Ischemia, Yuri M. Klyachkin, Anush V. Karapetyan, Mariusz Z. Ratajczak, Ahmed Abdel-Latif

Saha Cardiovascular Research Center Faculty Publications

Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI) and ischemic heart disease (IHD) remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 …

Reduction Of Vldl Secretion Decreases Cholesterol Excretion In Niemann-Pick C1-Like 1 Hepatic Transgenic Mice, Stephanie M. Marshall, Kathryn L. Kelley, Matthew A. Davis, Martha D. Wilson, Allison L. Mcdaniel, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Lawrence L. Rudel, J. Mark Brown, Ryan E. Temel

Saha Cardiovascular Research Center Faculty Publications

An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high …

Epc-Derived Microvesicles Protect Cardiomyocytes From Ang Ii-Induced Hypertrophy And Apoptosis, Shenhong Gu, Wei Zhang, Ji Chen, Ruilian Ma, Xiang Xiao, Xiaotang Ma, Zhen Yao, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Cell-released microvesicles (MVs) represent a novel way of cell-to-cell communication. Previous evidence indicates that endothelial progenitor cells (EPCs)-derived MVs can modulate endothelial cell survival and proliferation. In this study, we evaluated whether EPC-MVs protect cardiomyocytes (CMs) against angiotensin II (Ang II)-induced hypertrophy and apoptosis. The H9c2 CMs were exposed to Ang II in the presence or absence of EPC-MVs. Cell viability, apoptosis, surface area and β-myosin heavy chain (β-MHC) expression were analyzed. Meanwhile, reactive oxygen species (ROS), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS), and their phosphorylated proteins (p-Akt, p-eNOS) were measured. Phosphatidylinositol-3-kinase (PI3K) and NOS inhibitors were used …

Aortic Aneurysms In Loeys-Dietz Syndrome - A Tale Of Two Pathways?, Frank Davis, Debra L. Rateri, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by skeletal abnormalities, craniofacial malformations, and a high predisposition for aortic aneurysm. In this issue of the JCI, Gallo et al. developed transgenic mouse strains harboring missense mutations in the genes encoding type I or II TGF-β receptors. These mice exhibited several LDS-associated phenotypes. Despite being functionally defective, the mutated receptors enhanced TGF-β signaling in vivo, inferred by detection of increased levels of phosphorylated Smad2. Aortic aneurysms in these LDS mice were ablated by treatment with the Ang II type 1 (AT1) receptor antagonist losartan. The results from this …

Cardiovascular Aging In The Female F344xbn Rat Model, Jacqueline C. Fannin

Theses, Dissertations and Capstones

Despite continued advances in medical care, cardiovascular disease (CVD) remains the leading cause of death for American women [1]. Although humans and non-human primates are the only mammals to experience menses, rodent models are commonly used to study age-associated cardiovascular alterations due to similar ovarian aging, low expense, and short lifetime to investigate cardiovascular aging. Previous studies have found that aging in the female rodent is characterized by increased ventricular apoptosis, elevations in oxidative-nitrosative stress, ventricular remodeling, increased collagen content, mild systolic and diastolic dysfunction, and reduced occurrence of arrhythmias compared to males [2-7]. Similarly, age-associated alterations in the female …

Comparison Of Semi-Automated And Manual Measurements Of Carotid Intima-Media Thickening, Oscar Mac Ananey, G Mellotte, V Maher

Articles

Carotid intima-media thickening (CIMT) is a marker of both arteriosclerotic and atherosclerotic risks. Technological advances have semiautomated CIMT image acquisition and quantification. Studies comparing manual and automated methods have yielded conflicting results possibly due to plaque inclusion in measurements. Low atherosclerotic risk subjects (n = 126) were recruited to minimise the effect of focal atherosclerotic lesions on CIMT variability. CIMT was assessed by high-resolution B-mode ultrasound (Philips HDX7E, Phillips, UK) images of the common carotid artery using both manual and semiautomated methods (QLAB, Phillips, UK). Intraclass correlation coefficient (ICC) and the mean differences of paired measurements (Bland-Altman method) were used …

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …

Amlodipine Reduces Angii-Induced Aortic Aneurysms And Atherosclerosis In Hypercholesterolemic Mice, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Andrew J. Morris, Richard Charnigo, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: The purpose of this study was to determine effects of amlodipine, a dihydropyridine calcium channel blocker, on development of angiotensin II (AngII)-induced vascular pathologies.

METHODS AND RESULTS: Male LDL receptor -/- mice were infused with vehicle, amlodipine (5 mg/kg/d), AngII (1,000 ng/kg/min), or AngII + amlodipine for 4 weeks through osmotic pumps (n=10/group). Mice were fed a saturated fat-enriched diet for 1 week prior to pump implantation and during 4 weeks of infusion. Infusion of amlodipine resulted in plasma concentrations of 32 ± 2 ng/ml and 27 ± 2 ng/ml for mice in saline + amlodipine and AngII + …

Successful Long-Term Extracorporeal Cardiopulmonary Membrane Oxygenation Without Anti-Coagulation, Janissa Nair, Dorothea T. Watson Do, Rita Pechulis Md, Fccp, Nicholas M. Rini Pa-C, Timothy S. Misselbeck, Kenneth Miller Rrt, James K. Wu Md

Department of Surgery

No abstract provided.

Reactive Hyperemia Occurs Via Activation Of Inwardly Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear.

Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (K_IR) channels and Na⁺/K⁺-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans.

Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, …

Calpain-2 Compensation Promotes Angiotensin Ii-Induced Ascending And Abdominal Aortic Aneurysms In Calpain-1 Deficient Mice, Venkateswaran Subramanian, Jessica J. Moorleghen, Anju Balakrishnan, Deborah A. Howatt, Athar H. Chishti, Haruhito A. Uchida

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, …

Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner

Faculty Publications

Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 …

Sustained Safety And Effectiveness Of Paclitaxel-Eluting Stents For Femoropopliteal Lesions: 2-Year Follow-Up From The Zilver Ptx Randomized And Single-Arm Clinical Studies., Michael D Dake, Gary M Ansel, Michael R Jaff, Takao Ohki, Richard R Saxon, H Bob Smouse, Scott A Snyder, Erin E O'Leary, Gunnar Tepe, Dierk Scheinert, Thomas Zeller, Zilver Ptx Investigators

Heart and Vascular Articles

Objectives: A prospective, multinational randomized controlled trial (RCT) and a complementary single-arm study evaluated the 2-year safety and effectiveness of a paclitaxel-coated drug-eluting stent (DES) in patients with superficial femoral artery lesions. The RCT compared the DES with percutaneous transluminal angioplasty (PTA) and provisional bare-metal stent (BMS) placement.

Background: Local drug delivery for superficial femoral artery lesions has been investigated with the intent of limiting restenosis similarly to DES for the coronary arteries. One-year outcomes of DES in the superficial femoral artery are promising, but longer-term benefits have not been established.

Methods: In the RCT, patients were randomly assigned to …

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

Dissertations and Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury …

Cardiovascular Risk Factors Prevalent Among Filipino-Americans: A Cross-Sectional Study, Alona Angosta

Interdisciplinary Research Scholarship Day

Filipino Americans are the 2nd largest Asian subgroup in the United States and their leading cause of death is cardiovascular disease (CVD). Despite this, little is known about their prevalence of CVD risk factors. This study revealed that many Filipino Americans living in Clark County, Nevada are at risk of heart disease because of the presence of CVD risk factors. Intensive lifestyle modification and treatment are recommended to help decrease the prevalence of heart disease in this group and improve their overall health outcomes. Nurses and nurse practitioners are in excellent position to educate their Filipino American clients regarding heart …