Circulatory and Respiratory Physiology Commons^™

Platelet Cd36 Signaling Through Erk5 Promotes Caspase-Dependent Procoagulant Activity And Fibrin Deposition In Vivo, Moua Yang, Andaleb Kholmukhamedov, Marie L. Schulte, Brian C. Cooley, Na'il O. Scoggins, Jeremy P. Wood, Scott J. Cameron, Craig N. Morrell, Shawn M. Jobe, Roy L. Silverstein

Saha Cardiovascular Research Center Faculty Publications

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer …

New Faculty Mentoring In Respiratory Care Programs, Kristen L. Mchenry, Jim Lampley, Randy L. Byington, Donald W. Good, Stephanie R. Tweed

ETSU Faculty Works

Introduction: The purpose of this study was to identify mentoring practices of new faculty members in Commission on Accreditation for Respiratory Care (CoARC) accredited respiratory care programs in the U.S. and to identify the perceptions of program directors regarding the observed impact of program mentoring practices. Methods: The method for the study was quantitative non-experimental survey research. The survey instrument was an electronic questionnaire titled Respiratory Care Faculty (RCF) Mentoring Survey. The 25-item survey was divided into three dimensions: mentoring practices, mentor/mentee relationship, and perceptions of the impact of new faculty mentoring. Of the 410 possible program director …

Transplantation Of Thioredoxin-1 Exosomes In A Murine Model Of Hind-Limb Ischemia: A Novel Therapeutic Approach, Shubham Kanake

Honors Scholar Theses

Peripheral artery disease is one of the most prevalent cardiovascular diseases in the United States and worldwide. It is estimated that over 8 million people in the United States are affected with peripheral artery disease, and up to 40% of people over 80 years old may have some degree of the disease. Peripheral artery disease can increase one’s chances for having other cardiovascular co-morbidities such as coronary artery disease, among others. Current interventional strategies are endovascular treatments such as transluminal angioplasty and stenting, or in more advanced cases peripheral artery bypass grafting. Medical interventions focus on managing symptoms and treating …

In-Vitro Simulation Of Acute Ischemic Stroke, Paolo Garcia

Biomedical Engineering Undergraduate Honors Theses

Acute ischemic stroke (AIS) is a condition that involves the occlusion of a blood vessel within the brain, effectively preventing the passage of oxygen and nutrients. AIS is highly prevalent in the United States, where nearly 795,000 strokes happen per year and 87% of those are ischemic. From a medical standpoint, the obstructing clot can be removed with the use of a stroke retrieval device. However, a need arises for testing the aforementioned devices on a patient’s specific vascular geometries in order to increase the likelihood of a successful procedure. Outlined is a process for developing a physical simulation of …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Acute Pressor Response To Psychosocial Stress Is Dependent On Endothelium‐Derived Endothelin‐1, Brandon M. Fox, Bryan K. Becker, Analia S. Loria, Kelly A. Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in …

Venous Thromboembolism Risk Stratification Via Electronic Medical Record Classification, Shannon L. Carpenter, Laura Miller-Smith, Brittney Hunter, Ashley Duty, Justin Sheets, Yuri Tupa, Kate Gibbs

Posters

No abstract provided.

Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy, Justin M. Canada

Theses and Dissertations

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and …

Workplace Standing Desks And Arterial Stiffness, Ian Greenlund

Dissertations, Master's Theses and Master's Reports

Many jobs in today’s society require sitting at a desk with little physical activity. Individuals who engage in ten hours of sedentary behavior per day double their CVD risk. Standing desks are thought to decrease sedentary time and improve cardiovascular health. Acute use of standing desks is shown to lower PWV. However, chronic effects remain unknown. Forty eight participants qualified as seated (19 females, 5 males: age 41 ± 2 years, BMI 25 ± 1 kg/m²) or standing (21 females, 3 males: age 45 ± 2 years, BMI 25 ± 1 kg/m²) groups based on habitual …

Sedentary Time And The Cumulative Risk Of Preserved And Reduced Ejection Fraction Heart Failure: From The Multi-Ethnic Study Of Atherosclerosis, Brandi Scot Rariden

UNF Graduate Theses and Dissertations

ABSTRACT

Purpose: The purpose of this study was to examine the relationship between self-reported sedentary time (ST) and the cumulative risk of preserved ejection fraction heart failure (HFpEF) and reduced ejection fraction heart failure (HFrEF) using a diverse cohort of U.S. adults 45-84 years of age.

Methods: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects (52.9% female). All were free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with baseline ST and risk of overall heart failure (HF), HFpEF, and HFrEF. Weekly self-reported ST was dichotomized …

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Metabolic Regulation Of Myocardial Adaptation To Exercise., Andrew Alan Gibb

Electronic Theses and Dissertations

While the benefits of exercise affect several organs, a significant adaptive response occurs within the heart. Exercise promotes cardiac growth, increases angiogenesis, and enhances cardiac function and these adaptations are associated with a cardioprotective phenotype. Additionally, extensive evidence shows that exercise dynamically regulates myocardial metabolism. This can be attributed to both changes in hormonal stimulation, increases in bioenergetic demand, and the bioavailability of circulating substrates. However, it is unclear whether these changes in metabolism contribute to physiologic cardiac growth. We reason that exercise-induced changes in metabolism are required to balance the catabolic and anabolic reactions needed for growth. Specifically, we …

Influence Of Longitudinal Position On The Evolution Of Steady-State Signal In Cardiac Cine Balanced Steady-State Free Precession Imaging, Tyler J. Spear, Tori A. Stromp, Steve W. Leung, Moriel H. Vandsburger

Saha Cardiovascular Research Center Faculty Publications

Background: Emerging quantitative cardiac magnetic resonance imaging (CMRI) techniques use cine balanced steady-state free precession (bSSFP) to measure myocardial signal intensity and probe underlying physiological parameters. This correlation assumes that steady-state is maintained uniformly throughout the heart in space and time.

Purpose: To determine the effects of longitudinal cardiac motion and initial slice position on signal deviation in cine bSSFP imaging by comparing two-dimensional (2D) and three-dimensional (3D) acquisitions.

Material and Methods: Nine healthy volunteers completed cardiac MRI on a 1.5-T scanner. Short axis images were taken at six slice locations using both 2D and 3D cine bSSFP. 3D acquisitions …

Problems In Embalming: Cyanide Poisoning, Rebecca Majus

ASA Multidisciplinary Research Symposium

To inform funeral professionals, or anyone interested, what cyanide poisoning is, how death from it occurs, how to detect it in postmortem remains, how it poses a problem for embalmers, and what embalming techniques can be used to treat it.

Effect Of Intranasally Delivered Rh-Vegf165 On Angiogenesis Following Cerebral Hypoxia-Ischemia In The Cerebral Cortex Of Newborn Piglets., Amit Jain, Panagiotis Kratimenos, Ioannis Koutroulis, Amishi Jain, Amulya Buddhavarapu, Jahan Ara

Pediatrics Faculty Publications

Background: Vascular endothelial growth factor (VEGF) stimulates vascular genesis and angiogenesis. Cerebral Hypoxia-Ischemia (HI) leads to the reduction of vasculature in the cerebral cortex of newborn piglets.

Objective: The present study tests the hypothesis that post-hypoxia intranasal administration of recombinant human VEGF₁₆₅ (rh-VEGF165) for 3 days increases the vascular density in the cerebral cortex of newborn piglets without promoting neovascularization.

Design/Methods: Ventilated newborn piglets were divided into three groups (n = 5/group): normoxic (Nx), hypoxic-ischemic (HI), and HI treated with intranasal rh-VEGF165rh-VEGF165 (HI-VEGF). HI piglets were exposed to HI (0.05 FiO2) for 30 min. Recombinant h-VEGF165 (100 ng/kg) …

Variations In Practice Of Apnea Test For Brain Death: Review From A Multihospital Health Care System, Jeffrey Stein, Marvi V. Rijhwani, Ernesto Brauer

Journal of Patient-Centered Research and Reviews

Background: Ventilation encompasses both active and passive processes. Air is initially drawn into the lungs due to a negative intrathoracic pressure created using the respiratory muscles, most importantly the diaphragm. In contrast, expiration is the passive relaxation of the respiratory muscles. Oxygenation occurs when oxygen diffuses across the alveolar-capillary membrane. The ability to oxygenate without ventilation has been termed apneic diffusion oxygenation or apneic oxygenation. We believe it is crucial to keep alveoli open in order for adequate oxygenation to occur. This can be achieved with the aid of positive end-expiratory pressure (PEEP). We investigated this concept in patients who …

Relative Associations Of Age, Height, And Weight On Sinus Of Valsalva And Mid-Ascending Aorta: An Imaging And Epidemiology Study, Mirza Nubair Ahmad, Syed Haris Pir, Mirza Mujadil Ahmad, Sharmeen Hussaini, Bijoy K. Khandheria, A. Jamil Tajik, Khawaja Afzal Ammar

Journal of Patient-Centered Research and Reviews

Background: Prior studies show ascending aorta diameter varies with age, height and weight, but they did not evaluate relative influence of these variables on aortic diameter. Since height is genetically determined, and genetic disorders like Marfan syndrome are predominantly associated with sinus of Valsalva (SOV) dilation, we hypothesized height may have stronger association with SOV.

Purpose: Based on anecdotal observation, since age, weight and obesity are acquired attributes, we hypothesized age, weight and body mass index may have greater association with mid-ascending aorta (MAA) diameter, even in normal patients.

Methods: We evaluated echocardiographic studies of patients ≥ 15 years old …

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation …

Calpain Inhibition Attenuates Adipose Tissue Inflammation And Fibrosis In Diet-Induced Obese Mice, Latha Muniappan, Aida Javidan, Weihua Jiang, Shayan Mohammadmoradi, Jessica J. Moorleghen, Wendy S. Katz, Anju Balakrishnan, Deborah A. Howatt, Venkateswaran Subramanian

Saha Cardiovascular Research Center Faculty Publications

Adipose tissue macrophages have been proposed as a link between obesity and insulin resistance. However, the mechanisms underlying these processes are not completely defined. Calpains are calcium-dependent neutral cysteine proteases that modulate cellular function and have been implicated in various inflammatory diseases. To define whether activated calpains influence diet-induced obesity and adipose tissue macrophage accumulation, mice that were either wild type (WT) or overexpressing calpastatin (CAST Tg), the endogenous inhibitor of calpains were fed with high (60% kcal) fat diet for 16 weeks. CAST overexpression did not influence high fat diet-induced body weight and fat mass gain throughout the study. …

Inhibition Of Cholesterol Biosynthesis Through Rnf145-Dependent Ubiquitination Of Scap, Li Zhang, Prashant Rajbhandari, Christina Priest, Jaspreet Sandhu, Xiaohui Wu, Ryan E. Temel, Antonio Castrillo, Thomas Q. De Aguiar Vallim, Tamer Sallam, Peter Tontonoz

Saha Cardiovascular Research Center Faculty Publications

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show …

Therapeutic Challenges In A Case Of Psoriasis With Nail Onset, Mădălina I. Mitran, Cristina I. Mitran, Maria I. Sârbu, Vasile Benea, Mircea Tampa, Simona R. Georgescu

Journal of Mind and Medical Sciences

Nail psoriasis affects a large number of patients with psoriasis and has a major psychosocial impact. Furthermore, it may be regarded as a predictor of more severe forms of psoriasis and early sign of psoriatic arthritis. The clinical presentations vary depending on the structure affected (nail matrix or nail bed), the nail lesions may range from minor to severe, but they are not specific. Treatment is a challenge, in most cases the lesions being resistant to therapy. We present a rare case of psoriasis with nail onset in a 59-year-old woman. The nail involvement confined to the fingernails was severe, …

Is There A Utility For Qrs Dispersion In Clinical Practice?, Ionuț Donoiu, Georgică Costinel Târtea, Elibet Chávez-González

Journal of Mind and Medical Sciences

Prognostic markers derived from standard ECG have always been seductive. Increased dispersion of durations of the P wave, of the QRS complex, or of the QT interval has been associated with the risk of atrial fibrillation, ventricular arrhythmias, sudden cardiac death, as well as with a general negative prognosis in various settings. However, these markers have intrinsic and methodological issues that question their utility. This paper presents data supporting the utility of QRS dispersion in clinical practice. Our investigation shows that QRS dispersion is a simple electrocardiographic marker with potential value in the assessment of patients in a variety of …

The Dual Role Of Group V Secretory Phospholipase A2 In Pancreatic Β-Cells, Preetha Shridas, Victoria P. Noffsinger, Andrea C. Trumbauer, Nancy R. Webb

Saha Cardiovascular Research Center Faculty Publications

Purpose

Group X (GX) and group V (GV) secretory phospholipase A₂ (sPLA₂) potently release arachidonic acid (AA) from the plasma membrane of intact cells. We previously demonstrated that GX sPLA₂ negatively regulates glucose-stimulated insulin secretion (GSIS) by a prostaglandin E2 (PGE2)-dependent mechanism. In this study we investigated whether GV sPLA₂ similarly regulates GSIS.

Methods

GSIS and pancreatic islet-size were assessed in wild-type (WT) and GV sPLA₂-knock out (GV KO) mice. GSIS was also assessed ex vivo in isolated islets and in vitro using MIN6 pancreatic beta cell lines with or without GV sPLA …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

Multiple Path Particle Dosimetry For Prediction Of Mouse Lung Deposition Of Nanoaerosol Particles, Mohammed Ali

Technology Faculty Publications and Presentations

Nanoaerosolized particle (dia.<200 >nm) antibiotic inhalation therapy was tested to treat pneumonic tularemia in mice caused by Francisella novicida infection. Very limited experimental techniques are available to properly estimate inhaled doses and distribution of the drug inside the mouse lungs. To overcome this problem, computational simulation of particle deposition based on the Multiple Path Particle Dosimetry (MPPD) model was employed to simulate in vivo experimental conditions which included nasal breathing with whole body exposure to the antibiotic in the form of nano-aerosolized medicine. The deposition results were compared with several in vivo experimental data reported in literature; and satisfactory agreements …

Complete Versus Culprit Only Revascularization In St-Elevation Myocardial Infarction-A Perspective On Recent Trials And Recommendations, Gabriela Andries, Sahil Khera, Robert Timmermans, Wilbert Aronow

NYMC Faculty Publications

The presence of multivessel coronary artery disease (CAD) is strongly associated with higher 30-day mortality, reduced myocardial reperfusion success, reinfarction, and occurrence of major adverse cardiac events (MACE) at 1 year compared with single-vessel CAD. Despite higher morbidity and mortality in patients with ST-elevation myocardial infarction (STEMI) and coexistent multivessel CAD, major guidelines recommended against percutaneous coronary intervention (PCI) on non-culprit lesions at the time of primary PCI in patients with STEMI who are hemodynamically stable. The presence of multivessel CAD often poses a therapeutic dilemma for interventional cardiologists. A few larger scale randomized controlled trials (RCTs) and meta-analyses have …

Diagnostic Effectiveness Of High-Sensitivity Troponins, Sean R. Bodin, Jacqueline Ramirez

Physician Assistant Capstones, 2016 to 2019

Background: Acute myocardial infarctions (AMI) are a leading cause of death in the United States. The key to increasing survivability is early recognition to expedite the proper treatment modalities. In conjunction with the clinical presentation and electrocardiograms, the use of cardiac biomarkers is exponentially important in not only recognizing a cardiac event but also determining the extent of injury. Advancement in laboratory technology has led to the development of high-sensitive troponin (hs-troponin) assays which can detect smaller cardiac troponin serum levels compared to conventional troponin assays. This implies that the use of hs-troponin assays is more effective in the …

Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh

Electronic Theses and Dissertations

Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment). However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system …

Nicotinamide Phosphoribosyltransferase Promotes Pulmonary Vascular Remodeling And Is A Therapeutic Target In Pulmonary Arterial Hypertension., Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M. Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M. Camp, Haiyang Tang, Shui Q. Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F. Machado

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pulmonary arterial hypertension is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT) is a cytozyme that regulates intracellular nicotinamide adenine dinucleotide levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation, and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling and that inhibition of NAMPT could attenuate pulmonary hypertension.

METHODS: Plasma, mRNA, and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells from patients with pulmonary arterial hypertension and in the lungs of rodent models of pulmonary hypertension.Nampt+/- mice were …