Nehal N. Mehta

Last updated
Nehal N. Mehta
NHLBI-Dr. Nehal Mehta.jpg
Born (1975-11-30) November 30, 1975 (age 47)
Mumbai, India
Education George Washington University School of Medicine
University of Pennsylvania
Oxford University
George Washington University

Nehal N. Mehta, (born November 30, 1975) is an American cardiologist at the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Maryland where he studies the role of innate immunity and inflammation in the development of cardiovascular and metabolic diseases.

Contents

He is the first Lasker Clinical Research Scholar Awardee at the National Institutes of Health (NIH), [1] and is presently the head of the Laboratory of Inflammation and Cardiometabolic Disease at NHLBI, and Lasker Senior Investigator at NIH. [2]

Education and early career

Mehta was born in Mumbai; as a one-year-old, he moved to the United States. [3] Mehta attended the George Washington University's 7-year biomedical program and received his Bachelor of Arts in 1997 with Honors and Doctor of Medicine degree in 2001 with Distinction from the George Washington University School of Medicine & Health Sciences. [4] He spent time in 1997 studying Biochemistry at Oxford University, United Kingdom before starting medical school.

He then completed a residency in internal medicine, fellowship in cardiovascular diseases, nuclear cardiology, and a post-doctoral fellowship in genetic epidemiology at the Hospital of the University of Pennsylvania where he joined in 2007 as the director of the Inflammatory Risk in Preventive Cardiology. [5] Initially, Mehta focused on the role of inflammation in obesity and performed studies demonstrating that acute inflammation led to adipose inflammation. Then in 2009, he extended these findings by collaborating with Dr. Joel Gelfand to understand why psoriasis, an inflammatory skin disease increased risk for heart attack. [6] To characterize this link, Mehta received the first Lasker Clinical Scholar Award which moved his program from the University of Pennsylvania to the NIH. In 2012, the Albert and Mary Lasker Foundation and the NIH named him the inaugural Lasker Investigator, [1] enabling Mehta to create a laboratory focusing on the role of inflammation in cardiometabolic diseases at the NIH.

Career

Following epidemiological observations of accelerated heart attack risk in psoriasis, Mehta’s research program has spent the past decade dissecting why this may occur. Prior work demonstrated that both aortic vascular inflammation and coronary artery plaque occur about a decade earlier in psoriasis compared to non-psoriasis. [7] Furthermore, cholesterol transport is dysfunctional which in the face of systemic inflammation and immune dysregulation drives early cholesterol crystal formation. [8] His work has focused on trying to elucidate whether treatment of the skin disease in psoriasis can reverse vascular diseases. His most recent discovery that “treatment with systemic anti-inflammatory medications improve lipid-rich coronary plaque in inflammatory diseases such as psoriasis” earned him both an NIH Director’s Awards and an NHLBI Orloff Science Award.

Honors and awards

Mehta has been a visiting professor at many medical and research institutes around the world.

Notable publications

  1. Elnabawi YA,...Mehta NN. Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index. JAMA Cardiol. 2019 Jul 31. doi: 10.1001/jamacardio.2019.2589. [Epub ahead of print] PubMed PMID   31365032. [12]
  2. Gelfand JM,...Mehta NN. A Phase IV, Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U Trial). J Invest Dermatol. 2020 Jan;140(1):85-93.e2. doi: 10.1016/j.jid.2019.07.679. Epub 2019 Jul 19. PubMed PMID   31326395. [13]
  3. Elnabawi YA,...Mehta NN. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study. Cardiovasc Res. 2019 Mar 15;115(4):721-728. doi: 10.1093/cvr/cvz009. PubMed PMID   30721933. [14]
  4. Mehta NN, Shin DB, Joshi AA, et al. Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial. Circ Cardiovasc Imaging. 2018;11(6):e007394. doi:10.1161/CIRCIMAGING.117.007394. PubMed PMID   29776990 [15]
  5. Sajja AP,...Mehta NN. Potential Immunological Links Between Psoriasis and Cardiovascular Disease. Front Immunol. 2018;9:1234. Published 2018 Jun 1. doi:10.3389/fimmu.2018.01234. PubMed PMID   29910818 [16]
  6. Baumer Y,...Mehta NN. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis. JCI Insight. 2018;3(1):e97179. Published 2018 Jan 11. doi:10.1172/jci.insight.97179. PubMed PMID   29321372 [17]
  7. Mehta NN, Teague HL, Swindell WR, et al. IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis. Sci Rep. 2017;7(1):13831. Published 2017 Oct 23. doi:10.1038/s41598-017-14365-1. PubMed PMID   29062018 [18]
  8. Lerman JB,...Mehta NN. Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study. Circulation. 2017;136(3):263‐276. doi:10.1161/CIRCULATIONAHA.116.026859. PubMed PMID   28483812 [19]

Related Research Articles

<span class="mw-page-title-main">Low-density lipoprotein</span> One of the five major groups of lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.

<span class="mw-page-title-main">Atherosclerosis</span> Form of arteriosclerosis

Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. These lesions may lead to narrowing of the arteries' walls due to buildup of atheromatous plaques. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on which body parts(s) the affected arteries are located in the body.

<span class="mw-page-title-main">Arteriosclerosis</span> Thickening, hardening and loss of elasticity of the walls of arteries

Arteriosclerosis is a vascular disorder characterized by abnormal thickening, hardening, and loss of elasticity of the walls of arteries; this process gradually restricts the blood flow to one's organs and tissues and can lead to severe health risks brought on by atherosclerosis, which is a specific form of arteriosclerosis caused by the buildup of fatty plaques, cholesterol, and some other substances in and on the artery walls.

<span class="mw-page-title-main">C-reactive protein</span> Mammalian protein found in humans

C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells in order to activate the complement system via C1q.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

<span class="mw-page-title-main">Coronary thrombosis</span> Medical condition

Coronary thrombosis is defined as the formation of a blood clot inside a blood vessel of the heart. This blood clot may then restrict blood flow within the heart, leading to heart tissue damage, or a myocardial infarction, also known as a heart attack.

Stephen E. Epstein is the Head of Translational and Vascular Biology Research at the MedStar Heart and Vascular Institute, MedStar Washington Hospital Center and Clinical Professor of Medicine at the Georgetown University School of Medicine.

<span class="mw-page-title-main">Paul Ridker</span> Cardiovascular epidemiologist and biomedical researcher

Paul M. Ridker is a cardiovascular epidemiologist and biomedical researcher. He is currently the Eugene Braunwald Professor of Medicine at Harvard University and Brigham and Women's Hospital, where he directs the Center for Cardiovascular Disease Prevention. Ridker also holds an appointment as Professor in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health.

<span class="mw-page-title-main">Vascular disease</span> Medical condition

Vascular disease is a class of diseases of the vessels of the circulatory system in the body, including blood vessels – the arteries and veins, and the lymphatic vessels. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood and lymph vessels can cause a range of health problems that can sometimes become severe, and fatal. Coronary heart disease for example, is the leading cause of death for men and women in the United States.

<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

Endothelial lipase (LIPG) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland. The LIPG enzyme is a vital component to many biological processes. These processes include lipoprotein metabolism, cytokine expression, and lipid composition in cells. Unlike the lipases that hydrolyze Triglycerides, endothelial lipase primarily hydrolyzes phospholipids. Due to the hydrolysis specificity, endothelial lipase contributes to multiple vital systems within the body. On the contrary to the beneficial roles that LIPG plays within the body, endothelial lipase is thought to play a potential role in cancer and inflammation. Knowledge obtained in vitro and in vivo suggest the relations to these conditions, but human interaction knowledge lacks due to the recent discovery of endothelial lipase. Endothelial lipase was first characterized in 1999. The two independent research groups which are notable for this discovery cloned the endothelial lipase gene and identified the novel lipase secreted from endothelial cells. The anti-Atherosclerosis opportunity through alleviating plaque blockage and prospective ability to raise High-density lipoprotein (HDL) have gained endothelial lipase recognition.

<span class="mw-page-title-main">Myocardial infarction</span> Interruption of blood supply to a part of the heart

A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck or jaw. Often it occurs in the center or left side of the chest and lasts for more than a few minutes. The discomfort may occasionally feel like heartburn. Other symptoms may include shortness of breath, nausea, feeling faint, a cold sweat, feeling tired, and decreased level of consciousness. About 30% of people have atypical symptoms. Women more often present without chest pain and instead have neck pain, arm pain or feel tired. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure, an irregular heartbeat, cardiogenic shock or cardiac arrest.

<span class="mw-page-title-main">Dalcetrapib</span> Chemical compound

Dalcetrapib is a CETP inhibitor which was being developed by Hoffmann–La Roche until May 2012. The drug was aimed at raising the blood levels of HDL cholesterol. Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health.

<span class="mw-page-title-main">Oxycholesterol</span> Chemical compound

Oxycholesterol or 5,6-epoxycholesterol is a form of oxidized cholesterol implicated in atherosclerosis. It is commonly formed from the reaction of fats and oxygen during high temperature cooking such as frying.

<span class="mw-page-title-main">Seven Countries Study</span>

The Seven Countries Study is an epidemiological longitudinal study directed by Ancel Keys at what is today the University of Minnesota Laboratory of Physiological Hygiene & Exercise Science (LPHES). Begun in 1956 with a yearly grant of US$200,000 from the U.S. Public Health Service, the study was first published in 1978 and then followed up on its subjects every five years thereafter.

<span class="mw-page-title-main">Varespladib</span> Chemical compound

Varespladib is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2). The molecule acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation. From 2006 to 2012, varespladib was under active investigation by Anthera Pharmaceuticals as a potential therapy for several inflammatory diseases, including acute coronary syndrome and acute chest syndrome. The trial was halted in March 2012 due to inadequate efficacy. The selective sPLA2 inhibitor varespladib (IC50 value 0.009 μM in chromogenic assay, mole fraction 7.3X10-6) was studied in the VISTA-16 randomized clinical trial (clinicaltrials.gov Identifier: NCT01130246) and the results were published in 2014. The sPLA2 inhibition by varespladib in this setting seemed to be potentially harmful, and thus not a useful strategy for reducing adverse cardiovascular outcomes from acute coronary syndrome. Since 2016, scientific research has focused on the use of Varespladib as an inhibitor of snake venom toxins using various types of in vitro and in vivo models. Varespladib showed a significant inhibitory effect to snake venom PLA2 which makes it a potential first-line drug candidate in snakebite envenomation therapy. In 2019, the U.S. Food and Drug Administration (FDA) granted varespladib orphan drug status for its potential to treat snakebite.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

The Multi-Ethnic Study of Atherosclerosis is an ongoing medical study which aims to investigate the characteristics of subclinical atherosclerosis and other cardiovascular diseases, and to determine risk factors for its progression to the clinically overt form of these diseases. Sponsored by the National Heart, Lung and Blood Institute, MESA was begun in July 2000, and it follows a population-based sample of 6,814 American men and women aged 45 to 84, recruited from six field centers. The diverse sample consists of 38% White subjects, 28% African American, 22% Hispanic, and 12% Asian. Over 1,000 peer-reviewed papers have been published based on MESA and its 145 independent ancillary studies.

The BaleDoneen Method is a risk assessment and treatment protocol aimed at preventing heart attack and stroke. The method also seeks to prevent or reduce the effects of type 2 diabetes. The method was developed by Bradley Field Bale and Amy Doneen.

Joel M. Gelfand is an American dermatologist and epidemiologist at the University of Pennsylvania in Philadelphia, Pennsylvania. He currently serves as the James J. Leyden Professor in Clinical Investigation, the Vice Chair of Clinical Research, the director of the Psoriasis and Phototherapy Treatment Center, and the medical director of the Clinical Studies Unit in the Department of Dermatology at the Perelman School of Medicine at the University of Pennsylvania. He studies systemic comorbidities of psoriasis and much of his research has centered on the connection between cardiovascular disease and psoriasis.

References

  1. 1 2 3 Schubert, Charlotte (2012). "Turning point: Nehal Mehta". Nature. 488 (7411): 421. doi: 10.1038/nj7411-421a .
  2. ↑ "Principal Investigators". NIH Intramural Research Program.
  3. ↑ Dey, Amit (2018-04-01). "Nehal N. Mehta MD MSCE". European Heart Journal. 39 (13): 1050–1053. doi: 10.1093/eurheartj/ehy031 . ISSN   1522-9645. PMID   29618032.
  4. ↑ "Faculty Directory | The School of Medicine & Health Sciences | The George Washington University". www.gwumc.edu.
  5. ↑ "Nehal N. Mehta | Faculty | Members | Penn Institute for Immunology | Perelman School of Medicine at the University of Pennsylvania". www.med.upenn.edu.
  6. ↑ Gelfand, JM; Neimann, AL; Shin, DB; Wang, X; Margolis, DJ; Toxel, AB (2006). "Risk of myocardial infarction in patients with psoriasis". JAMA. 296 (14): 1735–1741. doi:10.1001/jama.296.14.1735. PMID   17032986. S2CID   631378.
  7. ↑ Lerman, JB; Joshi, AA; Chaturvedi, A; Aberra, TM; Dey, AK; Rodante, JA; Salahuddin, T; Chung, JH; Rana, A; Teague, H; Wu, J; Playford, MP; Lockshin, BA; Chen, MY; Sandfort, V; Bluemke, DA; Mehta, NN (2017). "Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study". Circulation. 136 (3): 263–276. doi:10.1161/CIRCULATIONAHA.116.026859. PMC   5534138 . PMID   28483812.
  8. ↑ Baumer, Yvonne; Dey, Amit K.; Gutierrez-Huerta, Cristhian A.; Khalil, Noor O.; Sekine, Yusuke; Sanda, Gregory E.; Zhuang, Jie; Saxena, Ankit; Stempinski, Erin; Elnabawi, Youssef A.; Dagur, Pradeep K.; Ng, Qimin; Teague, Heather L.; Keel, Andrew; Rodante, Justin A.; Boisvert, William A.; Tsoi, Lam C.; Gudjonsson, Johann E.; Bleck, Christopher K.E.; Chen, Marcus Y.; Bluemke, David A.; Gelfand, Joel M.; Schwartz, Daniella M.; Kruth, Howard S.; Powell-Wiley, Tiffany M.; Playford, Martin P.; Mehta, Nehal N. (2020). "Hyperlipidaemia and IFNgamma/TNFalpha Synergism are associated with cholesterol crystal formation in Endothelial cells partly through modulation of Lysosomal pH and Cholesterol homeostasis". eBioMedicine. 59: 102876. doi:10.1016/j.ebiom.2020.102876. PMC   7502673 . PMID   32646751.
  9. ↑ "Beaumont Research Honors Society". www.smhs.gwu.edu.
  10. ↑ "Orloff Science Awards". www.nhlbi.nih.gov.
  11. ↑ "Outstanding Investigator Award". AFMR.
  12. ↑ Elnabawi, YA; Oikonomou, EK; Dey, AK; Mancio, J; Rodante, JA; Aksentijevich, M; Choi, H; Keel, A; Erb-Alvarez, J; Teague, HL; Joshi, AA; Playford, MP; Lockshin, B; Choi, AD; Gelfand, JM; Chen, MY; Bluemke, DA; Shirodaria, C; Antoniades, C; Mehta, NN (2019). "Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index". JAMA Cardiology. 4 (9): 885–891. doi:10.1001/jamacardio.2019.2589. PMC   6669789 . PMID   31365032.
  13. ↑ Gelfand, JM; Shin, DB; Alavi, A; Torigian, DA; Werner, T; Papadopoulos, M; Takeshita, J; Noe, MH; Dey, AK; Playford, MP; Mehta, NN (January 2020). "A Phase IV, Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U Trial)". The Journal of Investigative Dermatology. 140 (1): 85–93.e2. doi:10.1016/j.jid.2019.07.679. PMC   6926160 . PMID   31326395.
  14. ↑ Elnabawi, YA; Dey, AK; Goyal, A; Groenendyk, JW; Chung, JH; Belur, AD; Rodante, J; Harrington, CL; Teague, HL; Baumer, Y; Keel, A; Playford, MP; Sandfort, V; Chen, MY; Lockshin, B; Gelfand, JM; Bluemke, DA; Mehta, NN (15 March 2019). "Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study". Cardiovascular Research. 115 (4): 721–728. doi:10.1093/cvr/cvz009. PMC   6432047 . PMID   30721933.
  15. ↑ Mehta, NN; Shin, DB; Joshi, AA; Dey, AK; Armstrong, AW; Duffin, KC; Fuxench, ZC; Harrington, CL; Hubbard, RA; Kalb, RE; Menter, A; Rader, DJ; Reilly, MP; Simpson, EL; Takeshita, J; Torigian, DA; Werner, TJ; Troxel, AB; Tyring, SK; Vanderbeek, SB; Van Voorhees, AS; Playford, MP; Ahlman, MA; Alavi, A; Gelfand, JM (June 2018). "Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial". Circulation: Cardiovascular Imaging. 11 (6): e007394. doi:10.1161/CIRCIMAGING.117.007394. PMC   5991103 . PMID   29776990.
  16. ↑ Sajja, AP; Joshi, AA; Teague, HL; Dey, AK; Mehta, NN (2018). "Potential Immunological Links Between Psoriasis and Cardiovascular Disease". Frontiers in Immunology. 9: 1234. doi: 10.3389/fimmu.2018.01234 . PMC   5992299 . PMID   29910818.
  17. ↑ Baumer, Y; Ng, Q; Sanda, GE; Dey, AK; Teague, HL; Sorokin, AV; Dagur, PK; Silverman, JI; Harrington, CL; Rodante, JA; Rose, SM; Varghese, NJ; Belur, AD; Goyal, A; Gelfand, JM; Springer, DA; Bleck, CK; Thomas, CL; Yu, ZX; Winge, MC; Kruth, HS; Marinkovich, MP; Joshi, AA; Playford, MP; Mehta, NN (11 January 2018). "Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis". JCI Insight. 3 (1). doi:10.1172/jci.insight.97179. PMC   5821196 . PMID   29321372.
  18. ↑ Mehta, NN; Teague, HL; Swindell, WR; Baumer, Y; Ward, NL; Xing, X; Baugous, B; Johnston, A; Joshi, AA; Silverman, J; Barnes, DH; Wolterink, L; Nair, RP; Stuart, PE; Playford, M; Voorhees, JJ; Sarkar, MK; Elder, JT; Gallagher, K; Ganesh, SK; Gudjonsson, JE (23 October 2017). "IFN-γ and TNF-α synergism may provide a link between psoriasis and inflammatory atherogenesis". Scientific Reports. 7 (1): 13831. Bibcode:2017NatSR...713831M. doi:10.1038/s41598-017-14365-1. PMC   5653789 . PMID   29062018.
  19. ↑ Lerman, JB; Joshi, AA; Chaturvedi, A; Aberra, TM; Dey, AK; Rodante, JA; Salahuddin, T; Chung, JH; Rana, A; Teague, HL; Wu, JJ; Playford, MP; Lockshin, BA; Chen, MY; Sandfort, V; Bluemke, DA; Mehta, NN (18 July 2017). "Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study". Circulation. 136 (3): 263–276. doi:10.1161/CIRCULATIONAHA.116.026859. PMC   5534138 . PMID   28483812.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.