Modeling patient-specific responses to
common calcium channel blockers using iPS cells
By Megan Mayerle
Advances in treatment strategies and therapeutics allow many individuals with chronic conditions a high quality of life. The symptoms of a wide variety of diseases can be mitigated simply by taking a pill. Many patients with hypertension are prescribed calcium channel blockers (CCBs) to control their blood pressure, which they take for the rest of their life. Although the acute effects of CCBs are well understood, very little is known about how these drugs impact cardiomyocyte physiology and gene expression patterns. Calcium is very important to heart cell function, and it is possible that CCBs could alter various cardiac cellular processes.
In a paper recently published in Circulation Research (May 2019), Stanford Cardiovascular Institute researchers led by instructor Chi Keung Lam used cardiomyocytes made from induced pluripotent stem cells (iPSC-CMs) isolated from three individuals to understand how four commonly prescribed CCBs (nifedipine, amlodipine, diltiazem, and verapamil) affected cardiomyocyte function in different people.
“iPSC technology allows us the opportunity to study how individual drugs will affect each patient, so we can decide on optimized, individualized treatment strategies”, Lam says.
Because they used multiple iPSC-CM cell lines isolated from different patients, Lam and colleagues were able to identify patient specific responses to each of the four CCBs tested. They were also able to determine a drug-specific gene expression signature for each CCB. Combining these findings, Lam and colleagues were able to pinpoint specific genes that could be used to predict how well individual hypertrophic cardiomyopathy patients would respond to verapamil, a specific CCB.
“Studies like this one are essential if precision medicine is to fulfill its promise”, says senior author Joseph C. Wu, who is professor and the director of the Stanford Cardiovascular Institute.
Other authors on this manuscript include Lei Tian, Nadjet Belbachir, Alexa Wnorowski, Rajani Shrestha, Ning Ma, Tomoya Kitani, and June Wha Rhee. Additional support was provided by the Stanford Neuroscience Microscopy Service (NIH P30 NS069375) and the Stanford Stem Cell FACS facility (NIH S10 RR029338). Funding was provided by NIH R01 HL113006, R01 HL128170, R01 HL130020, R01 HL126527; and American Heart Association grants 17MERIT33610009 and 19CDA34770040.