Regulating Calcium Could Help Regenerate the Heart

Blocking calcium could have a beneficial effect on the heart’s ability to regenerate myocardium in patients with ischemic heart failure, according to a new study published online in npj Regenerative Medicine.

Drugs that inhibit L-type calcium channels (LTCC) like nifedipine have long been used to treat hypertension, but preliminary research conducted by two separate groups had previously hinted that regulating the calcium pathway might also allow for better healing and cardiomyocyte proliferation in patients following MI.

‘‘[We’re pointing] out the role of something that’s been in use for forever, but nobody knew about it,” study co-author Tamer M. A. Mohamed, PhD (Baylor College of Medicine, Houston, TX), told TCTMD. “Now it has a good use.”

For their study, which was led by Lynn A. C. Devilée, MS (Queensland University of Technology, Brisbane, Australia), and senior author Riham Abouleisa, PhD (Baylor College of Medicine), the researchers show how both pharmacological and genetic inhibition of LTCC, using nifedipine and targeted gene therapy, respectively, modulate calcineurin activity and induce cardiomyocyte replication in both mice and lab-grown human cardiac organoids.

“What we found basically is that this calcium cycling that controls the contraction, if you turn it down a bit, . . . this can promote the healing process,” Mohamed explained. “This could be used for any heart failure patient.”

What’s “advantageous” about this approach over stem cell therapies is that it uses intrinsic tissue, thereby mitigating the issues with implantation rates of exogenous cells seen in prior research, according to co-author Todd Rosengart, MD (Baylor College of Medicine). “That’s a very significant positive,” he told TCTMD. “The negative, of course, is if the efficiency is going to be robust enough. . . .  This is a very high bar to regenerate enough myocardium to be able to impact global ejection fraction or global cardiac function.”

Another theoretical side effect to rule out will be promiscuous gene activation that leads to nontargeted effects, Rosengart added, noting that no studies so far have shown this to occur.

The investigators have begun studying this mechanism in larger animals and will focus on fine-tuning the dose of nifedipine to have the optimal effect in humans. “Optimization of the dosage is very important because too much of inhibition of calcium will basically stop the heart from contraction completely,” Mohamed said.