Pathway found to raise "good" cholesterol

Researchers have found a new target that may be the key to raising levels of "good" cholesterol--a hot topic in drug discovery circles. The team at Penn's School of Medicine found that a group of liver enzymes called proprotein convertases raise levels of HDL-C. The pathway involves another enzyme that normally degrades HDL-C, and was also discovered at Penn. 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. And the researchers say the same pathway should apply to humans. Proving that will be their next goal.

- here's the release on their work

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