Isaac Eliaz1, Elaine Weil1, Julie-Ann Dutton2, Audrey E McCalley2, Barbie Nolte3, Patrick M Moriarty2,3. 1. Amitabha Medical Clinic and Healing Center, Santa Rosa, California. 2. University of Kansas Medical Center, Atherosclerosis and Lipid-Apheresis Center, Kansas City, Kansas. 3. Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
Abstract
BACKGROUND: Plasma galectin-3 (Gal-3) is elevated in, and drives, diverse systemic inflammatory disorders, including cancer, cardiovascular diseases, and diabetes. Circulating Gal-3 promotes tumorigenesis and metastasis, as well as fibrotic remodeling, and is a promising therapeutic target. Apheresis has proven utility in reducing circulating disease-promoting substances, exemplified by the success of lipoprotein apheresis (LA) in abrogating cardiovascular disease progression in drug-refractory hypercholesterolemia patients. We compared the clinical utility of two FDA-approved LA systems in reducing plasma Gal-3 in humans. METHODS: Plasma Gal-3 levels were assessed by ELISA in blinded samples drawn pre- and post-apheresis from hypercholesterolemia patients (n = 10/group) undergoing therapeutic LA using either a heparin-induced extracorporeal LDL precipitation (HELP) or dextran sulfate-adsorption (DSA) system. RESULTS: Mean baseline plasma Gal-3 concentrations (±SD) were 14.3 ± 5.1 (range 6.6-22.8) and 14.5 ± 2.8 (range 10.6-19.8) ng/mL in the HELP and DSA groups, respectively. Post-apheresis Gal-3 levels were respectively reduced by 19.4% and 22.7% in the HELP (P = 0.0094) and DSA (P = 0.0027) systems (paired t-tests); the difference between devices was insignificant (P = 0.5288; Mann-Whitney). Post-treatment Gal-3 levels were 11.3 ± 3.7 (HELP; range 4.5-16.3) and 11.3 ± 3.8 (DSA; range 7.5-20.7) ng/mL. CONCLUSIONS: Circulating Gal-3 levels showed a statistically significant decrease in humans undergoing therapeutic LA. Although absolute Gal-3 reduction was ≈19-23%, this effect, combined with reducing atherogenic LDL and other inflammation mediators (e.g., CRP, fibrinogen, Lp-PLA2 ), may enhance apheresis clinical benefits. Applying new Gal-3-specific extraction technologies to apheresis may be advantageous in treating diverse pathologies that are promoted by elevated plasma Gal-3. J. Clin. Apheresis 31:388-392, 2016.
BACKGROUND: Plasma galectin-3 (Gal-3) is elevated in, and drives, diverse systemic inflammatory disorders, including cancer, cardiovascular diseases, and diabetes. Circulating Gal-3 promotes tumorigenesis and metastasis, as well as fibrotic remodeling, and is a promising therapeutic target. Apheresis has proven utility in reducing circulating disease-promoting substances, exemplified by the success of lipoprotein apheresis (LA) in abrogating cardiovascular disease progression in drug-refractory hypercholesterolemiapatients. We compared the clinical utility of two FDA-approved LA systems in reducing plasma Gal-3 in humans. METHODS: Plasma Gal-3 levels were assessed by ELISA in blinded samples drawn pre- and post-apheresis from hypercholesterolemiapatients (n = 10/group) undergoing therapeutic LA using either a heparin-induced extracorporeal LDL precipitation (HELP) or dextran sulfate-adsorption (DSA) system. RESULTS: Mean baseline plasma Gal-3 concentrations (±SD) were 14.3 ± 5.1 (range 6.6-22.8) and 14.5 ± 2.8 (range 10.6-19.8) ng/mL in the HELP and DSA groups, respectively. Post-apheresis Gal-3 levels were respectively reduced by 19.4% and 22.7% in the HELP (P = 0.0094) and DSA (P = 0.0027) systems (paired t-tests); the difference between devices was insignificant (P = 0.5288; Mann-Whitney). Post-treatment Gal-3 levels were 11.3 ± 3.7 (HELP; range 4.5-16.3) and 11.3 ± 3.8 (DSA; range 7.5-20.7) ng/mL. CONCLUSIONS: Circulating Gal-3 levels showed a statistically significant decrease in humans undergoing therapeutic LA. Although absolute Gal-3 reduction was ≈19-23%, this effect, combined with reducing atherogenic LDL and other inflammation mediators (e.g., CRP, fibrinogen, Lp-PLA2 ), may enhance apheresis clinical benefits. Applying new Gal-3-specific extraction technologies to apheresis may be advantageous in treating diverse pathologies that are promoted by elevated plasma Gal-3. J. Clin. Apheresis 31:388-392, 2016.