Nav: Home

UC-led study could bring about strategies to increase 'good' cholesterol

November 13, 2017

CINCINNATI -- After decades of individual attempts to identify the structure of the main building block of HDL (high-density lipoproteins), the so-called "good" cholesterol that associates with protection from cardiovascular disease, a research team representing eight academic institutions across the U.S. and Australia has come to agreement on a predictive model.

Their study, "A Consensus Model of Human Apolipoprotein A-I in its Monomeric and Lipid-Free State" is currently available online in the journal Nature Structure and Molecular Biology.

"We are excited to finally have a robust picture of what this protein looks like," says Sean Davidson, PhD, professor and vice chair in the Department of Pathology and Laboratory Medicine at the University of Cincinnati (UC) College of Medicine, and the corresponding author on the study.

Davidson and John Melchior, PhD, a UC postdoctoral fellow, organized a working group of leading lipid structural biologists to attack a fundamental issue in the field of fat metabolism. "All of us, including myself, have been chipping away at the edges of this problem for decades," says Davidson, adding that the protein simply doesn't respond to the typical methods used to model other protein structures.

Thus, the working group took a novel approach: they combined data from a variety of indirect experimental techniques from different laboratories to develop a consensus model. The breakthrough took over a year of intense cooperation among scientists who are normally in friendly competition. "This study was a unique collaborative experience for me. People from all over the U.S. and Australia freely shared what amounts to a couple of centuries (or more) of collective expertise and knowhow to come up with a definitive insight into apoA-I structure." says Kerry Anne-Rye, PhD, a co-author from the University of New South Wales in Australia.

A second factor, low-density lipoprotein (LDL), has been called "bad" cholesterol and can be harmful. While the body needs some cholesterol to function, when levels of LDL get too high, fatty deposits can accumulate in blood vessels. This causes them to narrow, leading to heart attacks, strokes or other serious vascular problems. HDL is thought to work against this accumulation.

Anchored by work that was awarded the Nobel Prize in 1985, the metabolism of LDL is well understood. This spurred the development of a class of drugs called statins which reduce "bad" cholesterol. However, the biology of HDL has been more elusive and this has complicated the development of HDL targeted drugs, says Davidson. "Our work, combined with the structure of a critical cell protein that helps assemble HDL published earlier this year, finally gives us the tools to propose and test hypotheses on how HDL is generated."
-end-
Also participating in the study were researchers Allison Cooke, Mark Castleberry and Jamie Morris from Davidson's laboratory. The working group included Ryan Walker and Tom Thompson, PhD, from the Department of Molecular Genetics Biochemistry and Microbiology at UC; Martin Jones, Hyun Song, PhD, and Jere Segrest, MD, PhD, from Vanderbilt University; Michael Oda, PhD, from Children's Hospital Oakland Research Institute; Mary Sorci-Thomas, PhD, and Michael Thomas, PhD, from the Medical College of Wisconsin; Jay Heinecke, MD, from the University of Washington; Xiaohu Mei, PhD, and David Atkinson, PhD, from Boston University; and Michael Phillips, PhD, and Sissel Lund-Katz, PhD, from the University of Pennsylvania.

This work was supported by an American Heart Association postdoctoral fellowship grant (16POST27710016 to Melchior), the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) funded pre-doctoral fellowship to Castleberry (HL125204-03), R01 HL127649 to Davidson, R01 HL127649 to Sorci-Thomas, P01 HL026335 and R01 HL116518 to Atkinson, P01 HL12803 to Davidson, Segrest and Heinecke. The mass spectrometry data was acquired in the UC Proteomics Laboratory under the direction of Ken Greis, PhD, on a mass spectrometer funded in part through an NIH S10 shared instrumentation grant (RR027015 Gries).

The authors have no conflicts of interest to report for this work

University of Cincinnati Academic Health Center

Related Cardiovascular Disease Articles:

Is educational attainment associated with lifetime risk of cardiovascular disease?
Men and women with the lowest education level had higher lifetime risks of cardiovascular disease than those with the highest education level, according to a new study published by JAMA Internal Medicine.
Food policies could lower US cardiovascular disease rates
New research conducted by the University of Liverpool and partners shows that food policies, such as fruit and vegetable subsidies, taxes on sugar sweetened drinks, and mass media campaigns to change dietary habits, could avert hundreds of thousands of deaths from cardiovascular disease (CVD) in the United States.
Cardiovascular disease causes one-third of deaths worldwide
Cardiovascular diseases (CVD), including heart diseases and stroke, account for one-third of deaths throughout the world, according to a new scientific study that examined every country over the past 25 years.
Kidney disease is a major cause of cardiovascular deaths
In 2013, reduced kidney function was associated with 4 percent of deaths worldwide, or 2.2 million deaths.
Cardiovascular disease costs will exceed $1 trillion by 2035
A new study projects that by 2035, cardiovascular disease, the most costly and prevalent killer, if left unchecked, will place a crushing economic and health burden on the nation's financial and health care systems.
Prescribing drugs for cardiovascular disease prevention in the UK
Drugs such as statins that have the potential to prevent strokes and other types of cardiovascular disease have not been prescribed to a large proportion of people at risk in the UK, according to a research article by Grace Turner of the University of Birmingham, Birmingham, UK and colleagues published in PLOS Medicine.
Fatty liver disease contributes to cardiovascular disease and vice versa
For the first time, researchers have shown that a bi-directional relationship exists between fatty liver disease and cardiovascular disease.
More dietary calcium may lower risk of cardiovascular disease
In older people, higher dietary calcium intake may lower the risk of cardiovascular disease, but not of stroke and fracture, new research from South Korea suggests.
Renal hemodynamics and cardiovascular function in health and disease
The SRC will focus on unpublished work that is state-of-the-art in study of cardiovascular and renal disease and hypertension.
Cardiovascular disease in adult survivors of childhood cancer
For adult survivors of childhood cancer, cardiovascular disease presents at an earlier age, is associated with substantial morbidity, and is often asymptomatic.

Related Cardiovascular Disease Reading:

Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty
by Leonard S. Lilly MD (Author)

Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 2-Volume Set, 11e
by Douglas P. Zipes MD (Author), Peter Libby MD PhD (Author), Robert O. Bonow MD MS (Author), Douglas L. Mann MD (Author), Gordon F. Tomaselli MD (Author)

Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based Therapeutics
by Y. Robert Li (Author)

Human Heart, Cosmic Heart: A Doctor’s Quest to Understand, Treat, and Prevent Cardiovascular Disease
by Dr. Thomas Cowan MD (Author)

Cardiovascular Disease: Fight it with the Blood Type Diet: The Individualized Plan for Treating Heart Conditions, High Blood Pressure, High ... Problems, and Angina (Eat Right 4 Your Type)
by Dr. Peter J. D'Adamo (Author), Catherine Whitney (Author)

Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, Single Volume, 11e
by Douglas P. Zipes MD (Author), Peter Libby MD PhD (Author), Robert O. Bonow MD MS (Author), Douglas L. Mann MD (Author), Gordon F. Tomaselli MD (Author)

Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors (The Report of the British Nutrition Foundation Task Force)
by British Nutrition Foundation (Author), Sara Stanner (Editor)

Cardiovascular Disease in Small Animal Medicine
by Wendy Ware (Author)

Cardiovascular Magnetic Resonance: A Companion to Braunwald’s Heart Disease, 3e
by Warren J. Manning MD (Author), Dudley J. Pennell MD FRCP FACC (Author)

Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 2-Volume Set, 10e
by Douglas L. Mann MD (Author), Douglas P. Zipes MD (Author), Peter Libby MD PhD (Author), Robert O. Bonow MD MS (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Why We Hate
From bullying to hate crimes, cruelty is all around us. So what makes us hate? And is it learned or innate? This hour, TED speakers explore the causes and consequences of hate — and how we can fight it. Guests include reformed white nationalist Christian Picciolini, CNN commentator Sally Kohn, podcast host Dylan Marron, and writer Anand Giridharadas.
Now Playing: Science for the People

#482 Body Builders
This week we explore how science and technology can help us walk when we've lost our legs, see when we've gone blind, explore unfriendly environments, and maybe even make our bodies better, stronger, and faster than ever before. We speak to Adam Piore, author of the book "The Body Builders: Inside the Science of the Engineered Human", about the increasingly amazing ways bioengineering is being used to reverse engineer, rebuild, and augment human beings. And we speak with Ken Thomas, spacesuit engineer and author of the book "The Journey to Moonwalking: The People That Enabled Footprints on the Moon" about...