Impact of cardiac shock wave therapy on the dynamics of biomarkers: results of proteomic analysis

Abstract

Background: Cardiac shock-wave therapy (CSWT) is a non-invasive treatment based on low-frequency ultrasound waves that stimulate angiogenesis. Current data on the effects of revascularization procedures on angiogenesis biomarkers are limited. In this study, we aimed to characterize the serum protein profiles of patients with coronary artery disease after CSWT treatment in relation to changes in exercise and imaging parameters. Methods: The study population included 10 patients from a prospective, randomized, triple-blind, sham-procedure controlled study (NCT02339454), who received CSWT and had demonstrated improvement in myocardial perfusion and/or contractility at 6 months follow-up The blood samples were collected at baseline, after the last treatment procedure (9th treatment week), at 6-month follow-up and stored at −80°C until analysis. The cardiovascular-related proteins (n=92) were measured using the Olink Proseek Multiplex Cardiovascular III panel (Olink, Uppsala, Sweden). Results: The median age was 65.5 years, and 7 patients were males. A total of 20 biomarkers showed significant changes from baseline to 9th week and 6 months follow-up (p<0.05). We identified 28 proteins that showed clear association with an increase in exercise tolerance and improvement in myocardial contractility or perfusion after CSWT. Using a volcano plot and results from the paired Mann-Whitney U test at confidence level of 0.95, we identified 3 proteins (PON3, TR-AP, CD163) with elevated values corresponding to increase in exercise duration (p<0.05) and 2 proteins (CPA1, COL1A1) related to improved myocardial contractility (p<0.05). A pathway analysis including 28 proteins suggested that these biomarkers were related to immune and inflammatory response, cell adhesion, tissue remodeling, proteolysis and catabolic processes. Conclusions: This study demonstrates the association of an increase in protein levels with an improvement in exercise duration and contractile function. Proteomic analysis suggests that CSWT exerts biological effects including immune and inflammation response, cell adhesion and tissue remodeling, all of which may mediate angiogenesis. Trial registration: Clinicaltrials.gov (NCT02339454).