Jonathan Smith, PhD, is the Geoffrey Gund Endowed Chair for Cardiovascular Research at Lerner Research Institute. With Cleveland Clinic since 2002, Smith has made major strides in his work toward cardiovascular excellence. Smith’s latest project involves an ApoA1 Exchange Rate Assay as a Diagnostic tool for Major Adverse Cardiovascular Events (MACE).
ApoA1 is a protein encoded by the ApoA1 gene, and is the major component of high-density lipoprotein (HDL). HDL cholesterol, or “good” cholesterol, transports certain fat molecules through the bloodstream, helping to remove them. Higher levels of HDL cholesterol enable better removal of fat and harmful cholesterol, and are therefore associated with a lower risk of heart disease. HDL, and its negative counterpart LDL, have long been good predictors of Major Adverse Cardiovascular Events. But newer studies indicate that HDL function, rather than HDL levels may be better predictors of heart disease. The existing method to measure HLD function is laborious and expensive, prompting Smith Smith to create something new.
The ApoA1 protein, though often bound in an HDL molecule, also exists lipid-free in the bloodstream. This unbound ApoA1 is periodically exchanged with the HDL-bound ApoA1; an important mechanism in the efflux of bad cholesterol. Smith and his colleagues developed an assay to measure the exchange rate of an exogenous tagged ApoA1 into HDL in clinical samples as an indicator of HDL function. With the development of their assay, Smith and team have learned that a higher rate of exchange indicates greater HDL function for a lower risk of heart disease and associated events.
Smith identifies 2018 as a breakout year for his assay as his lab began to see significant data. Through use of patient blood serum samples, they uncovered the inverse association between ApoA1 exchange and adverse cardiovascular events. All samples were provided by Dr. Stan Hazen from a cohort of angiography patients at Cleveland Clinic this past year. Recently, this assay has also been used with serum samples from patients enrolled in Cleveland Clinic’s infamous bariatric STAMPEDE trial. Data from this study is forthcoming.
In 2018, Smith submitted a patent application for the assay through Innovations. The technology has garnered interest from several companies, though no licensing deals have been made at this time. Looking forward, Smith hopes his assay can be used to screen for patients who may benefit from extensive treatment to improve HDL function. He also believes in use of the technology to identify candidates for cardiovascular drug trials. In 2019, he looks to replicate his findings in new cohorts and explore the possibility of collaboration with other institutions.