Lipoprotein Metabolism

The Lipoprotein Metabolism Laboratory, led by Dr. Alan T. Remaley, seeks to translate new insights gained from a wide range of studies spanning from basic science to clinical trials on lipoprotein metabolism into much-needed clinical advances in the diagnosis, treatment and prevention of cardiovascular disease, a common chronic disease and leading worldwide cause of death.

Alan Remaley

Senior Investigator Research Interests

Research Interests

Cardiovascular disease (CVD) is a common chronic disease caused by atherosclerosis that often first starts in childhood. In the United States, one person dies from CVD every 33 seconds, amounting to approximately 2,580 deaths per day. In 2022, an estimated 3.65 million deaths occurred worldwide due to cardiovascular disease.

Excess circulating cholesterol in the blood is one of the main drivers of atherosclerosis, which is the deposit of excess cholesterol into the arterial wall. Cholesterol, however, plays a vital role in normal cellular processes; hence, its cellular and whole-body distribution is subject to complex, dynamic regulation by circulating lipoproteins and enzymes. Dr. Remaley’s laboratory seeks to better understand lipoprotein metabolism and to translate new insights gained from basic biochemistry, cell biology, animal models and clinical trials into much needed clinical advances in the diagnosis, treatment and prevention of cardiovascular disease.

One focus of Dr. Remaley’s laboratory is on the beneficial role of high-density lipoprotein (HDL), the so-called “good cholesterol.” HDL, which is a complex of the protein apoA-I with phospholipids, removes excess cholesterol from peripheral tissues, such as the arterial wall, and transports it to the liver and intestine for excretion from the body. It has been shown that this process—the reverse cholesterol transport pathway—can be markedly stimulated by infusing HDL made with either purified or recombinant apoA-I and phospholipids. HDL infusion has been proposed as an acute therapy for patients with acute coronary syndrome who are at imminent risk for developing myocardial infarction. His laboratory has developed small synthetic peptide mimetics of apoA-I, and like the full-length protein, these peptides mobilize excess cholesterol from cells and have been shown to reduce atherosclerosis and inflammation in animal models and are currently being tested by his group in early-stage clinical trials.

Dr. Remaley’s laboratory also investigates “bad cholesterol”, in other words cholesterol that is transported on low-density lipoproteins (LDL). The deposition of LDL into the vessel wall is one of the main drivers of atherosclerosis, the underlying pathogenic process that leads to cardiovascular disease. Using CRISPR-Cas9 screening, his laboratory has identified new genes related to the cellular uptake of LDL. His group has also recently solved the structure of LDL and how it binds to its receptor using cryo-electron microscopy (cryoEM), which may lead to new therapeutic strategies for lowering LDL.

Another focus of the Lipoprotein Metabolism Laboratory is the development of new cardiovascular biomarkers. The lab has pioneered a method for calculating LDL cholesterol, which is now widely used in clinical laboratories worldwide for routine diagnostics of hypercholesterolemia.

In Dr. Remaley’s view, it is a privilege to work at the NIH and to have the opportunity to study and learn from patients at the NIH with both common and rare genetic disorders of cholesterol metabolism.  It often leads to new insights that cannot be obtained in any other manner and inspires him and his co-workers to translate their basic science findings in lipoprotein metabolism into new therapies and diagnostic tests for cardiovascular disease.

Videos

Images

Group photo of lab members.
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It takes a village to do good science” is a motto of Dr. Alan Remaley’s team of the Lipoprotein Metabolism Laboratory at NHLBI. “One of the best things about the NIH is that we get to work with top experts from across the U.S. and around the world to turn scientific discoveries into new cures for mankind. ”

Cover image of Science Translational Medicine. Illustration shows a simulation snapshot of D6PV peptide interacting with a trilayer of lipids.
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Cover page of the vol. 12, no. 528 issue of Science Translational Medicine journal that highlights a research article of Wolska et al. entitled “A dual apolipoprotein C-II mimetic-apolipoprotein C-III antagonist peptide lowers plasma triglycerides.” published in the journal in Jan 29, 2020, doi: 10.1126/scitranslmed.aaw7905.

Illustration shows a simulation snapshot of D6PV peptide interacting with a trilayer of lipids.

Dr. Alan Remaley and Maureen Sampson pointing at a blackboard displaying the Sampson Equation
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Dr. Alan Remaley and Maureen Sampson, a research Medical Technologist in the NIH Department of Laboratory Medicine, have shared their equation calculator for low-density lipoprotein cholesterol (LDL-C), called Sampson-NIH equation for LDL-C. It has been published in JAMA Cardiology and is available for free to researchers and clinicians to improve testing of LDL-C in patients at risk for heart diseases.

Other equations of the team are available at https://figshare.com/authors/Maureen_Sampson/9315995 and include Sampson-NIH equations for small dense LDL-C, phenotype algorithm, and enhanced VLDL-C equations.

“Through an estimated atherosclerotic cardiovascular disease risk score called eASCVD, we developed an adjunctive tool for the primary prevention of ASCVD that can also be used as a decision aid for statin therapy.” Anna Wolska, M.S., Ph.D., F.A.H.A. Staff Scientist, Laboratory of Lipoprotein Metabolism; NIH-NHLBI logo; Red Background. Headshot of Dr. Anna Wolska
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Determining atherosclerotic cardiovascular disease (ASCVD) risk is crucial for its prevention. M. Sampson and Dr. A. Wolska and colleagues have recently published a paper in Clinical Chemistry journal on a new estimated ASCVD risk score called eASCVD that can be automatically computed by clinical laboratories for all patients with a fasting standard lipid panel to improve the primary prevention of ASCVD. This research was featured by the NHLBI on their website in an article Calculating risks for heart disease | NHLBI, NIH Access to the free eASCVD calculator is available at https://figshare.com/articles/software/Sampson_eASCVD_equation_calculator/14222852

Clinical Trials and Studies

Recruiting
Adult, Older Adult
All Sexes
Accepting Healthy Volunteers
Are you interested in the heart-healthy benefits of omega-7 fatty acids? One of the most common types is palmitoleic acid. Researchers want to learn more about the potential benefits of these fatty acids, which can be found in certain fish and nuts. Participants must be at least 18 years old without known cardiovascular disease. This study is located at the NIH Clinical Center in Bethesda, Maryland.
Recruiting
Adult, Older Adult
All Sexes
Accepting Healthy Volunteers
Are you a healthy adult who is interested in helping researchers learn about heart disease? This study is testing a new medicine called Fx-5A that may be used to treat inflammation and various heart and blood vessel diseases. Participants will have an infusion of Fx-5A while researchers monitor the electrical activity of their heart using a non-invasive, painless heart test called an electrocardiogram (EKG). To participate in this study, you must not be pregnant or have any heart-related conditions. This study is located at the NIH Clinical Center in Bethesda, Maryland.
Recruiting
Adult, Older Adult
All Sexes
Not Accepting Healthy Volunteers
Are you a healthy adult who would like to help researchers learn about digestive and cardiovascular health? This study tests whether a synbiotic supplement can increase the type and amount of beneficial gut bacteria in healthy people as well as improve cardio-vascular protection markers. The supplement contains a natural sugar from human milk.

Meet the Team

Alan Remaley

Alan Remaley, M.D., Ph.D., FAHA

Senior Investigator

Dr. Remaley is the section chief of the Lipoprotein Metabolism Laboratory in the Translational Vascular Medicine Branch of the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Maryland. He is also a senior staff member of the Department of Laboratory Medicine at the National Institutes of Health Clinical Center.

Dr. Remaley received his BS in biochemistry and chemistry from the University of Pittsburgh in 1981. In 1987, he received an MD and PhD (biochemistry) from the University of Pittsburgh and completed in 1990 a residency in clinical pathology at the University of Pennsylvania. He did a post-doctoral fellowship with Dr. Bryan Brewer at NHLBI from 1990 to 1995.

He has been the recipient of many awards for his research and reached the rank of Captain in the United States Public Health Service before he joined the civil service in 2014. He has published more than 500 papers in the field of lipoprotein metabolism and cardiovascular disease. In addition, he is an inventor on multiple patents related to new therapeutic agents and diagnostic tests for cardiovascular disease.

The central focus of Dr. Remaley’s research is lipoprotein metabolism and its role in cardiovascular disease. As a physician-scientist, he uses a multidisciplinary approach to translate basic science findings into new therapies or diagnostics.