Medicine and Health Sciences Commons^™

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Student and Faculty Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …

Glp1 Receptor Agonists-Effects Beyond Obesity And Diabetes, Sydney S Wilbon, Mikhail G Kolonin

Student and Faculty Publications

Glucagon-like peptide-1 receptor agonists (GLP1RA) have been transformative for patients and clinicians in treating type-2 diabetes and obesity. Drugs of this class, the bioavailability of which is continuously improving, enable weight loss and control blood glucose with minimal unwanted side effects. Since adopting GLP1RA for treating metabolic diseases, animal and clinical studies have revealed their beneficial effects on several other pathologies, including cardiovascular diseases, neurodegeneration, kidney disease, and cancer. A notable commonality between these diseases is their association with older age. Clinical trials and preclinical data suggest that GLP1RA may improve outcomes in these aging-related diseases. Some of the benefits …

Risk Of Cancer After Diagnosis Of Cardiovascular Disease, Caitlin F Bell, Xiudong Lei, Allen Haas, Richard A Baylis, Hua Gao, Lingfeng Luo, Sharon H Giordano, Mackenzie R Wehner, Kevin T Nead, Nicholas J Leeper

Student and Faculty Publications

BACKGROUND: Cardiovascular disease (CVD) and cancer share several risk factors. Although preclinical models show that various types of CVD can accelerate cancer progression, clinical studies have not determined the impact of atherosclerosis on cancer risk.

OBJECTIVES: The objective of this study was to determine whether CVD, especially atherosclerotic CVD, is independently associated with incident cancer.

METHODS: Using IBM MarketScan claims data from over 130 million individuals, 27 million cancer-free subjects with a minimum of 36 months of follow-up data were identified. Individuals were stratified by presence or absence of CVD, time-varying analysis with multivariable adjustment for cardiovascular risk factors was …

Association Of Circulating Mtdna With Cvd In Hemodialysis Patients And In Vitro Effect Of Exogenous Mtdna On Cardiac Microvascular Inflammation, Zhen Fan, Ya Feng, Li Zang, Yi Guo, Xiao-Yi Zhong

Student and Faculty Publications

BACKGROUND: Chronic kidney disease (CKD) patients sustain a fairly high prevalence of cardiovascular disease (CVD). Microvascular inflammation is an early manifestation of CVD, and the released mitochondrial DNA (MtDNA) has been proposed to be a crucial integrator of inflammatory signals. Herein, the aim of this study was to determine the relationship between CVD, microvessel, and circulating MtDNA in the settings of uremia.

METHODS: Forty-two maintenance hemodialysis (MHD) patients and 36 health controls were enrolled in this study. Plasma cell-free MtDNA was detected by TaqMan-based qPCR assay. CVD risk markers including high-sensitive C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), fibrinogen, and …

A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin

Student and Faculty Publications

Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, …

The Innate Immune System In Cardiovascular Diseases And Its Role In Doxorubicin-Induced Cardiotoxicity, Anchit Bhagat, Pradeep Shrestha, Eugenie S Kleinerman

Student and Faculty Publications

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release …

A Critical Review Of Medication Adherence In Hypertension: Barriers And Facilitators Clinicians Should Consider, Seyed Mehrdad Hamrahian, Omar H. Maarouf, Tibor Fülöp

Department of Medicine Faculty Papers

Hypertension is a global public health problem, and its prevalence is increasing worldwide. Impacting all human societies and socioeconomic strata, it remains the major modifiable risk factor for global burden of cardiovascular disease all-cause mortality and the leading cause of loss of disability-adjusted life years. Despite increased awareness, the rate of blood pressure control remains unsatisfactory, particularly in low-to middle-income countries. Apparent treatment-resistant hypertension is associated with worse adverse health outcomes. It includes both true resistant and pseudo-resistant hypertension, which requires out-of-office blood pressure monitoring to exclude white-coat effect and confirmation of adherence to the agreed recommended antihypertensive therapy. The …

Cardiovascular Disease Awareness Program On Risk Factors For Cardiovascular Disease Among Adolescents In Selected Schools, In New Delhi, Komal Kumari

Manipal Journal of Nursing and Health Sciences

Introduction: Cardiovascular disease (CVD) is the main cause of mortality worldwide. The main risk factors include tobacco chewing/smoking, higher blood cholesterol, high blood pressure, physical inactivity, obesity, excessive alcohol use, age, sex, and heredity. Although CVDs commonly develop in middle age or later, risk factors are highly impacted by childhood practices that are continued into maturity. Knowledge gaps on CVD and its risk factors are major obstacles to effective prevention and treatment. Hence, a CVD awareness program was organized in order to educate adolescents about CVD and its risk factors. Objective: The objectives of the study were to identify students’ …

Yoke Between Covid-19 Infection And Cardiovascular Diseases: Evidence Briefing From Indian Studies, Melita Sheilini

Manipal Journal of Nursing and Health Sciences

Abstract:

Globally, Cardio[ES[M1] [m2] vascular diseases (CVDs) are of major concern. The current pandemic situation of COVID 19 infection has further hiked the burden of cardiovascular problems.

Since India has a large number of cases with cardiovascular problems the interlink between the COVID 19 infection and CVD has greatly challenged the field of medicine.[ES[M3] [m4] Also, the surge in COVID-19 cases in India hampered the regular follow-up of individuals with cardiovascular problems resulting in people seeking health care services only when the health condition gets deteriorated and in need of emergency medical aid. The main reason for this …

Evaluation Of Cardiovascular Changes In Patients With Gastric Wall Fat Halo Sign, Ali̇ Küpeli̇, Eser Bulut, Edhem Ünver, Gürkan Danişan

Turkish Journal of Medical Sciences

Background/aim: This study aims to investigate the relationship between gastric wall fat halo sign and potentially associated cardiovascular disease (CVD) in thoracic computed tomography (CT). Materials and methods: Between October 2020 and January 2021, 62 patients with gastric wall fat halo sign and 62 controls were evaluated with thorax CT. Patient's height, weight, body mass index (BMI), sex, age, comorbidities, laboratory parameters, diameters of cardiac axes, aorta and pulmonary artery; aorta and coronary artery calcium scores were recorded for the two groups. Results: No significant differences were found in sex, age, height, body weight or BMI between the two groups …

The Physiological Benefits Of A Plant-Based Diet On Cardiovascular Health, Jenevieve Petray

Nursing | Senior Theses

Cardiovascular disease (CVD) is increasingly more prevalent in today’s society and is attributed to an alarming percentage of American hospitalizations and deaths. Americans are unhealthier than ever before, and the main contributor is the Western diet. Diet is a double-edged sword that can offer benefits or detriments to one’s health. CVD encompasses numerous diagnoses originating from various underlying physiological alterations. These alterations are downstream effects of increased body weight and BMI, increased cholesterol levels, decreased insulin sensitivity and increased arterial plaque buildup. Research shows that a plant-based diet has the potential to manage and reverse all fundamental physiological alterations that …

Integrating Patient-Reported Outcomes Into Clinical Genetic Testing For Familial Hypercholesterolemia, Rachele M. Hendricks-Sturrup, Robert Block, Christine Y. Lu

Journal of Patient-Centered Research and Reviews

Patient-reported outcomes (PROs) and PRO measures (PROMs) are often used to help clinicians and researchers understand patients’ personal concerns, feelings, experiences, and perspectives following the implementation of an intervention. Notably, PROs and PROMs can inform health systems, health policy, and payers on the utility of clinical genetic testing based on each patient’s personal values, perspectives, and potential health behaviors subsequent to testing. In this topic synopsis, we discuss the underexplored role of and implications for PROs and PROMs following genetic testing for familial hypercholesterolemia (FH), an autosomal dominant genetic disorder of cholesterol metabolism that can lead to highly premature fatal …

Importance Of Pgc-1Α Gene Expression In Egyptian Hemodialysis Patients, Ashraf Donia, Azza A. I. Elmenyawi

Journal of Medicine in Scientific Research

Introduction The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is an upstream transcriptional regulator of mitochondrial biogenesis and function. Its function is immediate elimination of reactive oxygen species to get rid of their cellular destruction sequelae. Decreased PGC-1α count and less mitochondrial function take part in renal failure. COX6C gene encodes mitochondrial oxidative phosphorylation proteins. Reaction of excessive reactive oxygen species with linolenic acid results in malondialdehyde (MDA) as a breakdown product. It is an important marker for evaluating oxidative damage. Patients and methods A total of 58 hemodialysis (HD) patients in the National Institute of Urology and Nephrology and 20 …

The Visceral Adiposity Index, Lipid Accumulation Product, And Plasma Atherogenicindex Are Associated With Subclinical Atherosclerosis In Patients With Newly Diagnosedacromegaly, Mustafa Özbek, Murat Çalapkulu, Sema Hepşen, Muhammed Erkam Sencar, Hayri̇ Bostan, İlknur Öztürk Ünsal, Erman Çakal

Turkish Journal of Medical Sciences

Background /aim: Acromegaly is a rare chronic endocrine disorder, the active form of which is associated with an increased risk of cardiovascular and metabolic disease. Therefore, early diagnosis and treatment of cardiovascular diseases in acromegaly patients are important in terms of morbidity and mortality. The aim of this study was to determine whether the visceral adiposity index (VAI), lipid accumulation product (LAP), and plasma atherogenic index (PAI) are early cardiovascular risk markers in patients with active acromegaly. Materials and methods: The study included 45 patients newly diagnosed with acromegaly and 45 age-sex matched healthy control subjects. The VAI, LAP, and …

Therapeutic Efficacy Of Antioxidants In Ameliorating Obesity Phenotype And Associated Comorbidities, Steven Tun, Caleb James Spainhower, Cameron Lee Cottrill, Hari Vishal Lakhani, Sneha S. Pillai, Anum Dilip, Hibba Chaudhry, Joseph I. Shapiro, Komal Sodhi

Pharmacology, Physiology and Toxicology

Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox …

Myeloid-Specific Deficiency Of Pregnane X Receptor Decreases Atherosclerosis In Ldl Receptor-Deficient Mice, Yipeng Sui, Zhaojie Meng, Se-Hyung Park, Wei-Wei Lu, Christopher Livelo, Qi Chen, Tong Zhou, Changcheng Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Abstract The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^ΔMyeLDLR^−/−) to elucidate the role of macrophage PXR signaling in atherogenesis. The …

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 …

Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli

Electronic Thesis and Dissertation Repository

Elevated plasma lipoprotein(a) (Lp(a)) is the most prevalent heritable risk factor in the development of cardiovascular disease. The apolipoprotein(a) (apo(a)) component of Lp(a) is strongly implicated in the pathogenicity of Lp(a). It is hypothesized that the inflammatory potential of Lp(a)/apo(a) is mediated by the lysine binding ability of the apo(a) kringle IV10 (KIV10) domain, along with its covalently bound oxidized phospholipid (oxPL). Using targeted mutagenesis, two novel null alleles for the LPA gene that generate non-secretable apo(a) species have been identified, resulting from amino acid substitutions in the KIV10 domain. A potential mechanism by which KIV10 oxPL modification is enriched …

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 …

Plasma Thrombin-Activatable Fibrinolysis Inhibitor (Tafi) Antigen Levels In Acromegaly Patients In Remission, Mehmet Erdoğan, Mustafa Özbek, Erdem Akbal, Kemal Üreten

Turkish Journal of Medical Sciences

Background/aim: Acromegaly is associated with increased morbidity andmortality, mostly due to cardiovascular complications.Plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels are associated with coagulation/fibrinolysis and inflammation. Plasma TAFI may play a role in arterial thrombosis in cardiovascular diseases. In this study, it was aimed to evaluate the thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and homocysteine levels in patients with acromegaly and healthy control subjects.Materials and methods: Plasma TAFI antigen and homocysteine levels in 29 consecutive patients with acromegaly and 26 age-matched healthy control subjects were measured. All patients included in the study were in remission. The TAFIa/ai antigen in the plasma samples …

Vegetable Nitrate Intakes Are Associated With Reduced Self-Reported Cardiovascular-Related Complications Within A Representative Sample Of Middle-Aged Australian Women, Prospectively Followed Up For 15 Years, J.K. Jackson, Amanda J. Patterson, Lesley K. Macdonald-Wicks, Peta M. Forder, Lauren C. Blekkenhorst, Catherine P. Bondonno, Jonathan M. Hodgson, Natalie C. Ward, Carl Holder, Christopher Oldmeadow, Julie E. Byles, Mark A. Mcevoy

Research outputs 2014 to 2021

Nitric oxide (NO) facilitates anti-atherosclerotic effects. Vegetables are a major source of dietary nitrate. Experimental data indicates that dietary nitrate can significantly reduce major risk factors for atherosclerosis and subsequent cardiovascular disease (CVD), as nitrate can be metabolized to produce NO via the nitrate-nitrite-NO pathway. The purpose of this study was to prospectively investigate the association between habitual dietary nitrate intakes and the incidence of self-reported CVD-related complications within a representative sample of middle-aged Australian women (1946–1951 cohort of the Australian Longitudinal Study on Women’s Health). Women free from disease at baseline who had completed the food frequency questionnaire data …

Adiposity Predicts Pulse Pressure In Subjects With Chronic Kidney Disease: Data From The Modification Of Diet In Renal Disease, Preeya T. Shah Phd, Rebecca Martin, Juan R. Sanabria, Zeid Khitan Md, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro Md

Juan R. Sanabria

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in …

Adiposity Predicts Pulse Pressure In Subjects With Chronic Kidney Disease: Data From The Modification Of Diet In Renal Disease, Preeya T. Shah Phd, Rebecca Martin, Juan R. Sanabria, Zeid Khitan Md, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro Md

Zeid J. Khitan

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in …

Adiposity Predicts Pulse Pressure In Subjects With Chronic Kidney Disease: Data From The Modification Of Diet In Renal Disease, Preeya T. Shah Phd, Rebecca Martin, Juan R. Sanabria, Zeid Khitan Md, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro Md

Joseph I Shapiro MD

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

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 …

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Kevin M Rice

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. …

Efficacy Of Female Rat Models In Translational Cardiovascular Aging Research, Kevin M. Rice, J. C. Fannin, C. Gillette, Eric Blough

Eric Blough

No abstract provided.

Genome- And Cd4+ T-Cell Methylome-Wide Association Study Of Circulating Trimethylamine-N-Oxide In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn), Stella Aslibekyan, Marguerite R. Irvin, Bertha A. Hidalgo, Rodney T. Perry, Elias J. Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N. Hopkins, Michael A. Province, Hemant K. Tiwari, Jose M. Ordovas, Devin M. Absher, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels.

Methods and results: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans. TMAO was not associated with other plasma markers of cardiovascular disease, …

Emerging Roles Of Xenobiotic Detoxification Enzymes In Metabolic Diseases, Michael C. Petriello, Jessie B. Hoffman, Andrew J. Morris, Bernhard Hennig

Superfund Research Center Faculty Publications

Mammalian systems have developed extensive molecular mechanisms to protect against the toxicity of many exogenous xenobiotic compounds. Interestingly, many detoxification enzymes, including cytochrome P450s and flavin-containing monooxygenases, and their associated transcriptional activators [e.g. the aryl hydrocarbon receptor (AhR)], have now been shown to have endogenous roles in normal physiology and the pathology of metabolic diseases. This mini-review will focus on two such instances: the role of flavin-containing monooxygenase 3 (FMO3) in the formation of the cardiometabolic disease biomarker trimethylamine-N-oxide (TMAO) and the role of AhR as a sensor of endogenous ligands such as those generated by the gut microbiota. Understanding …