Researchers pinpoint why some don't respond to beta-blockers
New research may show why some heart failure patients don’t respond to beta-blocker drugs—with the cause lying in the dysfunction of beta-adrenergic receptor 3 (β3AR) and resulting decreases in cardioprotective phospholipid.
Led by Walter Koch, PhD, professor and chair of the department of pharmacology at the Lewis Katz School of Medicine at Temple University, the researchers examined S1P receptor 1 (S1PR1) downregulation in heart failure and the effects of metoprolol, a common beta-blocker.
The research was published July 3 in the Journal of the American College of Cardiology.
According to Koch, beta-blocker drugs increase S1P levels, with most drugs targeting β1ARs. The team mimicked heart failure in cells, while treating them with metoprolol. They found the drug had the opposite effect as isoproterenol triggered S1PR1 internalization, with receptors retreating from the front of cells to the interior.
"[The] drugs can also have stimulatory effects on β3AR, promoting β3AR activity," Koch said. "Our new work shows that when β3AR is dysfunctional, the protective effects of S1P are lost."
The Temple University team also showed mice treated with either metoprolol or S1P halted heart failure after heart attack. The S1P level remained low in β3AR patients despite treatment with metoprolol.
"Mechanistically, we've identified a novel means by which β1AR blockers prevent the progression of heart failure, whereby β3AR must be active for metoprolol to work," said Koch.
Nicholas joined TriMed in 2016 as the managing editor of the Chicago office. After receiving his master’s from Roosevelt University, he worked in various writing/editing roles for magazines ranging in topic from billiards to metallurgy. Currently on Chicago’s north side, Nicholas keeps busy by running, reading and talking to his two cats.