NALINI SANTANAM, PHD, MPH, FAHA
Department of Biomedical Sciences
Prof. Department of Cardiology (Medicine)
Coordinator, Cardiovascular Disease Research cluster
1700 3rd Ave, 435S BBSC
Joan C. Edwards School of Medicine, Marshall University
Huntington, WV 25755
REDOX REGULATION OF CARDIOMETABOLIC DISEASES
Cardiometabolic diseases are on the rise within the United States especially in the Appalachian region (West Virginia- 2nd highest). Cardiometabolic diseases (CMD) includes obesity, Type 2 diabetes and cardiovascular diseases. Lifestyle modifications (diet and exercise) can help to reduce risk to CMD by regulating appetite and preventing metabolic dysfunction. Regulating redox stress is a key mechanism by which lifestyle modifications prevent CMD. Altering the gut-microbiome axis may also be involved. Our research utilizes novel stress-less mouse models (BBA 1863:2293-2306) to alter redox balance and improve appetite and microbiota. We are studying the effects of diets (high saturated, PUFA or omega-3 fatty acid rich diets) or exercise on appetite regulation (adipose-brain-liver cross-talk), gut microbiota and cardiometabolic endpoints in these mouse models. ECHO-MRI, CLAMS, rodent treadmills, rodent ultrasound, next generation sequencing, miRNA microarray, Luminex technology, Ingenuity pathway analysis etc are some of the cutting edge techniques that are routinely used in our studies.
AGING AND ADIPOSE DYSFUNCTION
Aging increases risk to cardiometabolic diseases especially cardiovascular disease, insulin resistance leading to diabetes. Studies have shown a loss of adipose function with aging. Our studies using Aging rat models (Fischer 344 x Brown Norway hybrid rats-FBN) showed sex dependent changes in ectopic fat adipokine profile. Our studies further showed a loss in metabolic plasticity in preadipocytes (adipose derived stem cells) with aging. MicroRNAs that regulated adipocyte differentiation were dysfunctional (PLoS One, 2013, 8(3):e59238, J Physiol & Biochem, 2017, 73:215-224). Our NIH (NIA) funded study investigates the association between increased risk to insulin resistance during aging to changes in pathways that regulate microRNA biogenesis and function in the adipose tissue
EPICARDIAL FAT AND VASCULAR CROSS TALK
Cardiovascular disease rates are still highest in the Appalachian region. These high rates are attributed to high prevalence of obesity within this region. Increase in visceral/abdominal adiposity is a hallmark for obesity. However, increase in ectopic fat (deposition of fat in non-adipose tissue) increases risk to obesity-associated complications (coronary artery disease, insulin resistance, non-alcoholic fatty liver disease, etc). Increase in fat that surrounds the heart or vasculature (epicardial fat) is a marker for future cardiovascular events (Fig. 3 & 4).
Studies in our laboratory are investigating the role of epicardial/perivascular fat (the fat that surrounds the heart and the coronaries) in risk to cardiovascular diseases in animal models and humans with coronary artery disease (CAD) (in collaboration with Department of Cardiology & Thoracic Surgery). We are investigating the role of microRNA and epigenetic pathways in adipose dysfunction. Epicardial fat-cardiomyocyte cross talk studies are being conducted using animal models and ex-vivo cell culture models.
EPIGENETICS IN ENDOMETRIOSIS AND OVARIAN CANCER
Endometriosis is an inflammatory/epigenetic disorder affecting about 10% of young women. The classic symptoms are infertility and chronic pelvic pain. Typically this pain is treated with non-steroidal anti-inflammatory drugs (NSAIDs), or with drugs that address the hormonal aspects of the disorder. Research from our laboratory over the past 20 years has shown the importance of oxidative stress in the etiology of both endometriosis and its associated pain (Pain, 2015, 156(3):528-39; Redox Biol, 2017, 12:956-966). Our clinical studies have shown the beneficial effects of antioxidant therapy (Vitamin E & C) in lowering the pain associated with endometriosis (Transl Res. 2013;161(3):189-95; Reprod. Sci. 2017;24:619-626). In collaboration with the Department of Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University we are investigating mechanisms involved in endometriosis-associated pain with the hope of uncovering more effective treatment options. We are using novel techniques in the fields of redox biology and epigenetics to produce new therapeutic options (Fig. 5). Endometriosis increases risk to ovarian cancer. In collaboration with the Edwards Comprehensive Cancer Center, Marshall University, we are studying the role of peritoneal microenvironment on endometriosis related ovarian cancer. We are studying epigenetic pathways that link endometriosis and ovarian cancer (Fig. 6).
TRANSLATIONAL STUDIES IN PROGRESS
1. Epicardial Fat Biomarkers: WV-Appalachian Heart Study. In collaboration with Department of Medicine (Cardiology) and Department of Cardiothoracic Surgery, St. Mary’s Heart Center, Huntington, WV.
2. Epigenetics, Oxidative Stress and Endometriosis associated pain: In collaboration with Department of Gynecology and Obstetrics, Cabell Huntington Hospital, Huntington, WV.
3. MiRNA & Technology Based Intervention In Diabetic Patients (TEACH Clinical Trial): In collaboration with Department of Endocrinology (Medicine) and Appalachian Translational Research Network.
4. Role of epigenetics in endometriosis associated ovarian cancer: In collaboration with Edwards Comprehensive Cancer Center.
1. Ray K2, Fahrmann J2, Mitchell B, Paul D, King H#, Crain C#, Cook C, Golovko M, S. Brose#, S. Golovko and Santanam N. Oxidation-sensitive nociception involved in endometriosis associated pain. (2015) Pain, 156(3):528-39.
2. Gary O Rankin and Nalini Santanam. Editorial Overview: Cardiovascular and renal: Recent advances, novel treatments and new targets for cardiovascular and renal diseases. (2016) Curr Opin Pharmacol, 27:iv-vi.
3. Nalini Santanam, Nathaniel Zonereich4 and Sampath Parthasarathy. Myeloperoxidase, as a potential target in women with endometriosis undergoing IVF. (2017) Reproductive Sci. 24 (4):619-626.
4. Caitlin Kocher#, Matthew Christiansen4, Sarah Martin#, Christopher Adams4, Paulette Wehner, Todd Gress and Nalini Santanam. Sexual dimorphism in obesity-related genes in the epicardial fat during aging. (2017) J. Physiol & Biochem, doi: 10.1007/s13105-016-0542-0. 73:215-224.
5. Kristeena Ray Wright2a, Brenda Mitchell, Nalini Santanam. Redox regulation of microRNAs in endometriosis-associated pain. (2017) Redox Biology, 12:956-966.
6. Mose July4, Saba Faiz4, Abid Yaqub, Prasanna Santhanam, Jillian Douglas4, Ronald Stanek, Todd Gress, Omolola Olajide, Henry Driscoll and Nalini Santanam. Role of adipokines and inflammatory markers in postmenopausal hypertension. (2017) Minerva Endocrinologica doi: 10.23736/S0391-1977.17.02595-0.
7. Deborah L. Amos2, Tanner Robinson#, Melissa B. Massie#, Carla Cook, Alexis Hoffsted#, Courtney Crain4, Nalini Santanam. Overexpression of catalase modulates metabolic parameters in leptin-deficient mice. (2017) BBA Molecular Basis of Disease 1863:2293-220. doi: 10.1016/j.bbadis.2017.06.016.
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