Cardiology Commons^™

Liposomal Delivery Of Azithromycin Enhances Its Immunotherapeutic Efficacy And Reduces Toxicity In Myocardial Infarction, Ahmed Al-Darraji, Renée R. Donahue, Himi Tripathi, Hsuan Peng, Bryana M. Levitan, Lakshman Chelvarajan, Dalia Haydar, Erhe Gao, David Henson, John C. Gensel, David J. Feola, Vincent J. Venditto, Ahmed K. Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We …

Sod2 Deficiency In Cardiomyocytes Defines Defective Mitochondrial Bioenergetics As A Cause Of Lethal Dilated Cardiomyopathy, Sudha Sharma, Susmita Bhattarai, Hosne Ara, Grace Sun, Daret K. St. Clair, Md Shenuarin Bhuiyan, Christopher Kevil, Megan N. Watts, Paari Dominic, Takahiko Shimizu, Kevin J. Mccarthy, Hong Sun, Manikandan Panchatcharam, Sumitra Miriyala

Toxicology and Cancer Biology Faculty Publications

Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O2^•-) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 (SOD2Δ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the …

Effect Of Niacin Monotherapy On High Density Lipoprotein Composition And Function, Scott M. Gordon, Marcelo J. Amar, Kianoush Jeiran, Michael Stagliano, Emma Staller, Martin P. Playford, Nehal N. Mehta, Tomas Vaisar, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL's cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function.

METHODS: A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL …

Heart Failure In Humans Reduces Contractile Force In Myocardium From Both Ventricles, Cheavar A. Blair, Elizabeth A Brundage, Katherine L. Thompson, Arnold J. Stromberg, Maya Guglin, Brandon J Biesiadecki, Kenneth S. Campbell

Statistics Faculty Publications

This study measured how heart failure affects the contractile properties of the human myocardium from the left and right ventricles. The data showed that maximum force and maximum power were reduced by approximately 30% in multicellular preparations from both ventricles, possibly because of ventricular remodeling (e.g., cellular disarray and/or excess fibrosis). Heart failure increased the calcium (Ca²⁺) sensitivity of contraction in both ventricles, but the effect was bigger in right ventricular samples. The changes in Ca²⁺ sensitivity were associated with ventricle-specific changes in the phosphorylation of troponin I, which indicated that adrenergic stimulation might induce different effects …

Characterizing Recurrence Following Hybrid Ablation In Patients With Persistent Atrial Fibrillation, David C. Kress, Lynn Erickson, Tadele W. Mengesha, David Krum, Jasbir Sra

Journal of Patient-Centered Research and Reviews

Purpose: It is It is widely accepted that atrial fibrillation (AF) accounts for half of arrhythmia recurrences following endocardial catheter ablation of AF. An epicardial-endocardial approach (hybrid) has emerged as an alternative to endocardial ablation alone for the treatment of AF, yet recurrence after a hybrid procedure has not been well characterized. This retrospective study is aimed at characterizing recurrence following hybrid ablation for patients with persistent AF.

Methods: Patients with persistent AF (N = 108) received both endocardial and epicardial ablation of the posterior left atrial wall using catheter ablation and a small midline surgical approach (hybrid). Presence of …

Endocrine Significance Of Sars-Cov-2'S Reliance On Ace2, Eric Lazartigues, Mirza Muhammad Fahd Qadir, Franck Mauvais-Jarvis

School of Medicine Faculty Publications

The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and …

Efficacy Of A Novel Mitochondrial-Derived Peptide In A Porcine Model Of Myocardial Ischemia/Reperfusion Injury, Thomas E. Sharp, Zhenwei Gong, Amy Scarborough, Eric S. Goetzman, Murtuza J. Ali, Pablo Spaletra, David J. Lefer, Radhika H. Muzumdar, Traci T. Goodchild

School of Medicine Faculty Publications

With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac …

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell

Internal Medicine Faculty Publications

Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca²⁺ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was …

Microrna-148a Regulates Low-Density Lipoprotein Metabolism By Repressing The (Pro)Renin Receptor, Na Wang, Lishu He, Hui Lin, Lunbo Tan, Yuan Sun, Xiaoying Zhang, A. H. Jan Danser, Hong S. Lu, Yongcheng He, Xifeng Lu

Saha Cardiovascular Research Center Faculty Publications

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR …

Investigating Medical Examiners' Practices: Genetic Evaluation For Fatal Acute Aortic Dissection, Bradley Power

Dissertations and Theses (Open Access)

Acute thoracic aortic dissection (TAD) is a life-threatening event with a hereditary component. Currently, pathogenic variants in 11 genes associated with aortic aneurysm and dissection predispose to a heritable form of disease thereby conferring an increased risk for TAD. Genetic testing plays a pivotal role not only in diagnosis, but also in risk stratification for relatives and medical management to prevent premature death from dissection. Due to its high fatality rate, medical examiners and coroners (ME/Cs) may be the first to identify TAD cases and initiate genetic testing for the decedent and at-risk relatives. ME/Cs were surveyed using three clinical …

Myocardial Work Index: A Novel Method For Assessment Of Myocardial Function In South Asian Recreational Athletes, Shantanu Sengupta, Renuka Jain, Nitin Burkule, Susan Olet, Bijoy K. Khandheria

Journal of Patient-Centered Research and Reviews

Purpose: We used a novel noninvasive method based on speckle-tracking echocardiography to evaluate myocardial performance in South Asian recreational athletes who completed a half marathon.

Methods: Transthoracic echocardiography was performed on 24 recreational athletes 48 hours before they took part in a half marathon (premarathon), within 2 hours of half marathon completion (postmarathon), and 72 hours after completion. Clinical, laboratory, and echocardiographic variables were collected. Speckle-tracking echocardiography was performed in all subjects to characterize myocardial mechanics.

Results: Mean age of participants was 41.8 ± 7.4 years, and 23 (95.8%) were male. No subject had a prior history of coronary artery …

Tetralogy Of Fallot: A Clinical Review, Jacob Wooten, Joshua Bahos Silva

Student Scholar Showcase

Tetralogy of Fallot is a congenital heart disease that is associated with structural abnormalities during fetal development 1. The incidence of Tetralogy of Fallot in the United States is approximately 3-5 cases per 10,000 live births and is considered one of the most common cyanotic congenital heart diseases 2. The exact etiology of Tetralogy of Fallot is unknown, however it is thought to be associated with untreated maternal diabetes, maternal use of retinoids, as well as chromosomal abnormalities 2. The main components of this disease state include a right ventricular outflow obstruction, interventricular communication in the form of a ventricular …

Regenerative Medicine Therapy: Adipose Derived Extracellular Vesicles In Viral Myocarditis, David Gorelov, Damian N. Di Florio, Gary R. Salomon, Angita Jain, Nick E. Saikaili, Danielle J. Beetler, Swikriti Shrestha, Ming Tian, Joy Wolfram Phd, Delisa Fairweather Phd, Katelyn Bruno Phd, Judith D. Ochrietor Phd

Showcase of Osprey Advancements in Research and Scholarship (SOARS)

Objective: Myocarditis, inflammation of the heart muscle, is an autoimmune heart disease that can be caused by viruses, bacteria and toxins. Myocarditis can lead to dilated cardiomyopathy (DCM) and heart failure. Currently there are no disease-specific therapies for treating myocarditis or preventing progression to DCM. Adipose Extracellular Vesicles (AEVs) are lipid bilayer nanoparticles that are released into the outside environment of adipocytes and provide promising regenerative potential for inflammatory diseases like myocarditis.

Methods: Lipoaspirate was obtained from women and men and AEVs isolated from the lipoaspirate using tangential flow filtration. We injected wild type male BALB/c mice with 250uL AEVs …

Flying After Diving: Decompressions And Barotraumas., Nihad E. Daidzic

Aviation Department Publications

FAA Safety Seminar (GL1598968) held at Modern Avionics/Air Trek North at KFCM, Eden Prairie, MN at 9:00 CST on Saturday, February 29, 2020.

The Role Of Interleukin-18 In Myocardial Ischemia/Reperfusion, Yogesh Dhakal

Theses and Dissertations

Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity for cardiovascular diseases (CVDs) in the western world. While mortality rates for AMI has reduced in the last 20 years due to advancements in clinical interventions, patients who have an AMI are significantly more likely to develop heart failure (HF) in the following years. Reperfusion of the ischemic tissue is a necessary procedure to restore blood delivery to cardiomyocytes, minimize myocardial dysfunction, and reduce infarct size. Still, the step of reperfusion itself induces myocardial damage in a phenomenon known as reperfusion injury. Considering that the degree of myocardial …

Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber

Articles, Abstracts, and Reports

Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed …

Biomarkers Of Inflammation In Heart Failure Patients With Reduced And Preserved Ejection Fractions: Multi-Ethnic Study Of Atherosclerosis, Michelle Lynne Stone

UNF Graduate Theses and Dissertations

Purpose Examine the relationships between high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor-α receptor-1 (sTNF-R1) and the cumulative risk of heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fractions in a diverse, population-based sample. Methods Study sample included 6,814 adult (45-84 years of age) men and women who participated in the Multi-Ethnic Study of Atherosclerosis and were free of cardiovascular disease at baseline. Cox regression was used to calculate the hazard ratios (HR) associated with elevated baseline hs-CRP (> 3-10 mg/L), IL-6 (> 75^th percentile) and sTNF-R1 (> 75^th percentile) and risk of overall …

The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan

Electronic Theses and Dissertations

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …

Changes In Ventricular Depolarisation Vectors During Exercise Caused By Regional Myocardial Ischaemia, Cameruddin Vellani, Satwat Hashmi, Sadia Mahmud, Mohammad Yusuf, Safia Awan, Khawar Kazmi

Section of Cardiology

Research at the Aga Khan University for several years has been directed to find a reliable, low-cost, portable, non-invasive method for identification of coronary artery disease, its location and extent. A new method has been devised to measure the magnitude and direction of cardiac electrical vectors in three perpendicular planes during physical exercise to identify reduction in myocardial excitability as the electrophysiological marker of hypoxia. This report shows that changes in electrical forces due to exercise-induced regional hypoxia serve as indicators of reversible myocardial ischaemia. Changes in the magnitude and direction of vectors at stages of the Bruce protocol were …

Comparison Of Long-Term Oral Anticoagulation Therapies Including Newly Approved Reversal Agent For Dabigatran, Mackenzie Devine, Natalie Lennartz, Michaela Wolford, Rebecca Worden, Joelle Farano, Erin Petersen

Pharmacy and Wellness Review

Anticoagulants are a well-known class of agents essential for the prevention of blood clots, which may further develop into deep vein thrombosis, pulmonary embolism or stroke. Individuals at a high risk of clotting, such as those with atrial fibrillation, multiple risk factors or recent hip/knee surgery, are in need of long-term anticoagulation therapy. The purpose of this review is to highlight the pros and cons for each available anticoagulant as well as discuss pivotal clinical trials that evaluated the safety and efficacy of these agents. Warfarin, the oldest anticoagulant, requires the patient to attend frequent appointments with a health care …

Triple Therapy Or Triple Threat: An Analysis Of Triple Antiplatelet Therapy Compared To Dual Antiplatelet Therapy, Isabel E. Cwikla, Kara C. Horvath, Elaina Gollmar, Austin Hilverding, Erin Petersen

Pharmacy and Wellness Review

Triple antiplatelet therapy (TAPT, or triple therapy), is an oral medication regimen designed to reduce the risk of major cardiovascular events. It consists of aspirin, clopidogrel or an alternative, and an oral anticoagulant (OAC). It differs from dual antiplatelet therapy (DAPT) due to inclusion of an OAC. Multiple clinical studies have indicated that triple therapy is more effective at clot prevention, when compared to aspirin monotherapy and DAPT, but is associated with a higher risk of major bleeding. Pharmacists have a key role in determining candidates for DAPT and TAPT regimens. Other opportunities for pharmacists include patient monitoring, counseling and …

Pcsk9 Inhibitors: A Novel Class Of Pharmacotherapy For Hypercholesterolemia, Angela Chu, Austin Hilverding, Elizabeth Kramer, Brendan Rasor, Boyd Rorabaugh

Pharmacy and Wellness Review

The recent U.S. Food and Drug Administration (FDA) approval of two new drugs, alirocumab (Praluent®) and evolocumab (Repatha®) is a breakthrough in the treatment of familial hypercholesterolemia. These drugs are a part of a new class called the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that act by increasing the number of low density lipoprotein receptors (LDL-R) recycled to hepatocyte membranes. The increased density of LDL-R facilitates greater clearance of low density lipoproteins from the blood. Numerous clinical trials have demonstrated the efficacy of these agents, particularly for patients in whom standard cholesterol-lowering therapy is insufficient. However, data on long-term …

Combined Neprilysin And Angiotensin Inhibitor For The Treatment Of Heart Failure, Albert Bui, Victoria Cho, Rebecca Worden, Haley Armstrong, Rachel Pucel, Lindsey Peters

Pharmacy and Wellness Review

Heart failure (HF) is a highly prevalent disease state worldwide that can progress into a disabling condition. It is pertinent to have a treatment regimen that is effective in lowering the number of HF exacerbations and, therefore, hospital readmission rates. A novel medication currently in clinical trials, LCZ696, blocks both neprilysin and angiotensin type I receptors. The overall effects are an inhibition of the breakdown of natriuretic peptides which leads to a decrease in renin and aldosterone release. This, combined with the antagonization of angiotensin type I receptors, leads to a decrease in blood pressure, blood volume and systemic vascular …

New Cholesterol Guidelines: An Update For Pharmacists, Emily Limberg, Benjamin Finley, Stacy Henthorne, Sarah Kradel, David Bright

Pharmacy and Wellness Review

The American College of Cardiology and American Heart Association published new blood cholesterol guidelines in November 2013. The new guidelines place an emphasis on evidence-based treatment of dyslipidemias and primarily use randomized controlled trials to create recommendations for health care providers. Major changes from the previous guidelines include eliminating low-density lipoprotein goals, the classification of statins by lipid-lowering potential and the creation of four major statin benefit groups. The new guidelines also establish the role of non-statins in dyslipidemias and use the Pooled Cohort Risk Assessment Equations to calculate patients' risk for cardiovascular events and the need for cholesterol-lowering medications. …

A Comparison Of Mipomersen (Kynamro®) And Lomitapide (Juxtapid®): Medications For The Treatment Of Homozygous Familial Hypercholesterolemia, Ann Marie Ruhe, Austin Brown, Ginny Daniels, Kelsey Fink, David Bright

Pharmacy and Wellness Review

Homozygous familial hypercholesterolemia (HoFH) is a rare disease that involves mutations in the genes coding for low density lipoprotein (LDL) receptors, preventing the uptake of LDL cholesterol from the serum and resulting in extremely high cholesterol levels.1 Between December 2012, and January 2013, two orphan drugs were approved by the U.S. Food and Drug Administration (FDA) for the treatment of HoFH. Mipomersen (Kynamro®) is a subcutaneous injection that functions as an antisense oligonucleotide inhibitor and ultimately prevents the translation of mRNA coding for apolipoprotein B (apoB)-100 which binds to LDL and very low density lipoprotein (vLDL) cholesterol.7 Lomitapide (Juxtapid®) is …

Novel Oral Anticoagulants: A Comparative Study Of The Clinical Potential For Dabigatran, Rivaroxaban, And Apixaban Versus Warfarin, Lindsay Mark, Joanne Tran, Zachary Jones, Jessica Beck, David Bright

Pharmacy and Wellness Review

Although Coumadin® (warfarin) has been the standard outpatient anticoagulant for long-term prevention of thrombosis for many decades, it presents with significant challenges for both patients and health care providers in optimizing standards of care including dietary and drug restrictions, regular monitoring of the patient's International Normalized Ratio (INR), and difficulty maintaining therapeutic levels. Despite its unmistakable effectiveness, there has been an interest from the medical community in developing potential alternative drug therapies. As a result, within the past three years the U.S. Food and Drug Administration (FDA) has approved the use of three new oral anticoagulant drugs (dabigatran, rivaroxaban, and …

Sildenafil As An Appropriate Monotherapy Option In The Treatment Of Pulmonary Arterial Hypertension (Pah), Kaitlin Horton, Kent Wilin, Sarah Ginty, Lara Long, David Bright

Pharmacy and Wellness Review

Pulmonary arterial hypertension (PAH) is a debilitating disease characterized by constriction in the diameter of the pulmonary arterial lumen.1,2 This leads to increased pressure and stress on the right ventricle of the heart, which may lead to heart failure and death.2,3 Currently there are only a few treatment options for patients with PAH. Sildenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, can be used to treat PAH. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP). Increased cGMP concentration results in pulmonary vasculature relaxation. Current clinical trials have indicated that sildenafil can significantly improve many of the symptoms of PAH. The …

A Population Pharmacokinetic Model For Simvastatin And Its Metabolites In Children And Adolescents., Kayode Ogungbenro, Jonathan B. Wagner, Susan M. Abdel-Rahman, J Steven Leeder, Aleksandra Galetin

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Poor adherence to dietary/behaviour modifications as interventions for hypercholesterolemia in paediatric patients often necessitates the initiation of statin therapy. The aim of this study was to develop a joint population pharmacokinetic model for simvastatin and four metabolites in children and adolescents to investigate sources of variability in simvastatin acid exposure in this patient population, in addition to SLCO1B1 genotype status.

METHODS: Plasma concentrations of simvastatin and its four metabolites, demographic and polymorphism data for OATP1B1 and CYP3A5 were analysed utilising a population pharmacokinetic modelling approach from an existing single oral dose (10 mg < 17 years and 20 mg ≥ 18 years) pharmacokinetic dataset of 32 children and adolescents.

RESULTS: The population PK model included …

Hdl Subclass Proteomic Analysis And Functional Implication Of Protein Dynamic Change During Hdl Maturation, Yuling Zhang, Scott M. Gordon, Hang Xi, Seungbum Choi, Merlin Abner Paz, Runlu Sun, William Yang, Jason Saredy, Mohsin Khan, Alan Thomas Remaley, Jing-Feng Wang, Xiaofeng Yang, Hong Wang

Saha Cardiovascular Research Center Faculty Publications

Recent clinical trials reported that increasing high-density lipoprotein-cholesterol (HDL-C) levels does not improve cardiovascular outcomes. We hypothesize that HDL proteome dynamics determine HDL cardioprotective functions. In this study, we characterized proteome profiles in HDL subclasses and established their functional connection. Mouse plasma was fractionized by fast protein liquid chromatography, examined for protein, cholesterial, phospholipid and trigliceride content. Small, medium and large (S/M/L)-HDL subclasseses were collected for proteomic analysis by mass spectrometry. Fifty-one HDL proteins (39 in S-HDL, 27 in M-HDL and 29 in L-HDL) were identified and grouped into 4 functional categories (lipid metabolism, immune response, coagulation, and others). Eleven …