Researchers at the University of Pennsylvania School of Medicine have discovered that a group of liver enzymes called proprotein convertases (PCs) may be the key to raising levels of good cholesterol (HDL-C).
Several PC enzymes, called furin, PACE4, and PCSK5A, disable another enzyme called endothelial lipase by clipping off a piece of it and by activating its inhibitor, which promotes an increased level of HDL-C in the blood.
The study appears in the current issue of Cell Metabolism.
Researchers at the University of Pennsylvania School of Medicine have discovered that a group of liver enzymes called proprotein convertases (PCs) may be the key to raising levels of good cholesterol (HDL-C). The pathway by which these proteins are able to achieve an increase in HDL cholesterol involves another enzyme that normally degrades HDL-C, and was also discovered at Penn. The newly recognized relationship between these enzymes and cholesterol represents another target for ultimately controlling good cholesterol. The study appears in the current issue of Cell Metabolism.
“Several PC enzymes, called furin, PACE4, and PCSK5A, disable another enzyme called endothelial lipase by clipping off a piece of it and by activating its inhibitor,” says first author Weijun Jin, MD, Research Assistant Professor of Pharmacology. “This promotes an increased level of HDL-C in the blood.”
“We showed that mice engineered to express high levels of PCSK5A had 50 percent higher HDL-C than control mice,” says senior author Daniel J. Rader, MD, the Cooper/McLure Professor of Medicine and Associate Director of the Institute for Translational Medicine and Therapeutics at Penn.
Increased HDL-C is due to decreased endothelial lipase (EL) activity. “This is encouraging because it suggests that either the PC or EL enzyme might be targets for drug therapy to raise good cholesterol, an unmet medical need in patients with low HDL-C,” says Rader. What’s more, the increase in HDL-C was shown to promote reverse cholesterol transport, the process by which HDL protects against heart disease.
Low levels of HDL-C put people at risk for atherosclerosis, thereby increasing the risk of heart attack and stroke. Although this study was performed in mice, humans have the same proprotein convertases and endothelial lipase, and these enzymes are conserved in all vertebrates. Jin and Rader expect that the same pathway for controlling HDL-C will apply to humans.
The next step is to study how the genes for the PCs, EL itself, and EL’s inhibitor are regulated. In addition, Jin and Rader plan to test whether variation in blood levels of PCs and EL activity in humans, as well as genetic variation in their genes, is associated with variation in HDL-C levels and heart disease risk.
“We hope to identify polymorphisms in the genes for PCs, EL, and its inhibitor that are associated with HDL-C levels, thus supporting that this pathway is relevant in humans,” says Rader.
Co-authors are Xun Wang, John S. Millar, and Jane M. Glick from Penn and Thomas Quertermous (Stanford University) and George H. Rothblat (Children’s Hospital of Philadelphia). The study was funded by the National Heart, Lung, and Blood Institute and the American Heart Association.
Karen Kreeger | EurekAlert!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences